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Respiratory function after cardiopulmonary bypass: A comparison of bubble and membrane oxygenators
Respiratory Function After Cardiopulmonary Bypass: A Comparison of Bubble and Membrane Oxygenators W.G. Reeve, FRCA, SM. Ingram, FRCRadiol, D.C. Smith, FRCA A consecutive sample of 500 adults undergoing cardiac surgery was randomly allocated to extracorporeal circulation with either a Bard bubble oxygenator H1700 or a Bard membrane oxygenator HF5700 (Bard Ltd. Crawley, UK). Alveolar-arterial oxygen tension gradient (AaDOJ was calculated prebypass, then 20,90, 180, and 420 minutes postbypass. Preoperative, initial postoperative, and first-day postoperative chest x-rays were assigned an extravascular lung water (EVLW) score and an atelectasis score. There was a comparable increase in AaDO after bypass in each group. The increase in EVLW score was significantly greater in the bubble group (mean 2.91, 95% Cl 2.28-3.54) than the membrane group (mean 2.06, 95% Cl 1.43-2.89) for the initial postoperative x-rays (P < 0.01) and also for the x-rays on the first postoperative day (P < 0.01). The increase in atelectasis
T
HERE ARE several consequences of cardiopulmonary bypass that may be more common when a bubble oxygenator is used than when a membrane oxygenator is used. These include microembolic retinal ischemia,1,2 damage to erythrocytes and platelets,3-7 with consequent bleeding and transfusion requirement, 8,yincrease in serum creatinine,lO requirement for inotropic support,lO complement activation,” activation of neutrophil granulocytes,3J0J2 transpulmonary sequestration of leukocytes,“J” and postbypass neutropenia.” Complement activation increases lung endothelial permeability14 causing pulmonary dysfunction. Neutrophil activation may also contribute to pulmonary dysfunction.3J3,15 Lung leukocyte and platelet sequestration and extravascular lung water are increased after bubble oxygenation in dog lungs,” but in a study of 30 patients there was no difference in EVLW measured by the double indicator dilution method between oxygenator types.16 Previous studies comparing the influence of oxygenator type on intrapulmonary shunt have given differing results,4,5J0J6-18so the clinical importance of any difference between oxygenator types is not known. The aim of this study was to determine whether there is a clinical difference in respiratory function between patients in whom a bubble oxygenator is used during bypass and patients in whom a membrane oxygenator is used. PATIENTS AND METHODS A consecutive sample of 500 adults undergoing cardiac surgery requiring cardiopulmonary bypass was studied after ethical committee approval was obtained. Exclusion criteria were (1) patients with intracardiac shunting and (2) whether the surgeon or anesthesiologist preferred to use a particular oxygenator for clinical reasons. Patients were randomly allocated to cardiopulmonary bypass
From Western Infirmary, Glasgow, Scotland. Address reprint requests to W G. Reeve, FRCA, Consultant Anaesthe&, Division of Anaesthesia, Royal Infirma y, Glasgow, G3I ZER, Scotland. Copyright 0 1994 by W.B. Saunders Company 1053-0770/9410805-0004$03.00/O
502
score was significantly greater in the bubble group (mean 1.08,95% Cl 0.94-1.18) than the membrane group (mean 0.86, 95% Cl 0.74-0.98) for the initial postoperative
x-rays (P c 0.01)
but not for the x-rays on the first postoperative was no difference
in duration of ventilation,
day. There
intensive care,
hospital stay, or hospital mortality between bubble and membrane groups. Although there was a statistically significant difference in x-ray scores between neither intrapulmonary
shunting
oxygenator
groups,
nor clinical outcome
influenced by the type of oxygenator
was
used during bypass.
Copyright 8 1994 by W.B. Saunders Company KEY WORDS: respiratory function, cardiopulmonary
bypass,
oxygenator
with either a Bard bubble oxygenator H1700 (bubble group) or a Bard hollow fiber membrane oxygenator HF5700 (membrane group). Bypass management was otherwise identical in both groups. The bypass circuit was primed with two liters of Hartmann’s solution to which was added 10 g of mannitol and 50 mmol of sodium bicarbonate. The flow index was 2.4 L/minim2 at 37°C reducing to 1.8 L/minim2 at 26 to 28°C. Alpha-stat acid-base control was used, and CO2 was added to the gas flow in the bubble oxygenator group. The first of the main outcome measures was alveolar-arterial oxygen tension gradient (AaDO?). Arterial blood gases were taken prebypass then 20, 90, 180, and 420 minutes postbypass. The fractional inspired oxygen concentration (F102) was also measured using a calibrated fuel cell. The alveolar partial pressure of oxygen (PA02) was calculated using the following equation: PA02
PaC02 = P102 - 7
1-R
+
I
PaC02.
FIOz.
-g-I
where P,Oz = inspired partial pressure of oxygen, PaC02 = arterial partial pressure of carbon dioxide, and R = respiratory exchange ratio, assumed to be 0.82. For each time point AaDO was calculated. The magnitude of this gradient is proportional to the intrapulmonary shunt. Other outcome measures were extravascular lungwater (EVLW) and atelectasis scores. Preoperative, initial postoperative, and first day postoperative chest x-rays were reviewed by a radiologist blinded to the type of oxygenator used. Each x-ray was assigned an EVLW scorei and an atelectasis score (Fig 1). Repeatability of the EVLW and atelectasis scores was assessed on a random sample of 53 of the x-rays used in the study. Additional outcome measures were duration of postoperative artificial ventilation, duration of stay in intensive care (ICU). and hospital outcome. The final outcome data were other perioperative factors that could have influenced postoperative respiratory function, which were obtained from the patients notes. These included a preoperative history of respiratory disease, pulmonary function tests, smoking history, New York Heart Association (NYHA) classification, left ventricular (LV) function, medication, operative procedure, bypass and aortic cross-clamp times, minimum patient temperature during bypass, and postoperative fluid balance. Decreased LV function was defined as a preoperative LVEDP greater than 18 mmHg or an ejection fraction less than 30%. Statistical analysis was performed using the Minitab 7 statistics package (Minitab Inc). Statistical tests included the unpaired
Journalof Cardiothoracic and VascularAnesthesia,
Vol8,
No 5 (October),
1994: pp 502.508
OXYGENATORS
AND THE LUNGS
503
Table 2. Perioperative Extravascular Lung Water
ScorC
Chest X-ray finding
mild
and Atelectasis Scores
c
EVLW Score
marked
Atelectasis confined to one quadrant
0.5
1.0
Atelectssis in two quadrants
1.0
2.0
Initial
Atelectasis in three qua&ants
1.5
3.0
First Day
Atelectasis in all four quadrants
2.0
4.0
Preoperative postoperative Postoperative
Atelectasis
Score
Bubble
Membrane
Bubble
Membrane
0.0 (0.0-2.0)
0.0 (0.0-3.0)
0.0 (0.0-0.0)
0.0 (0.0-0.0)
3.5 (11.0-7.0) 3.0 (0.0-7.0)
1.0 (0.0-2.0)
1.0 (0.0-2.0)
2.0 (0.0-5.0)
2.0 (1 .O-2.0) 2.0 (1 .O-2.0)
1 .O (0.0-4.0)
NOTE. Median (interquartile range).
Mann-Whitney U test, x2 test, Spearman rank correlation and Kruskal-Wallis as appropriate. Results are quoted as mean (*SD) unless otherwise stated.
t-test, Fig 1.
Atelectasis scoring system.
RESULTS
Three hundred sixty-five (73%) coronary bypass procedures and 135 (27%) valve replacements were studied. The two groups were comparable for age, sex, height, weight, body surface area, NYHA grade, and LV function (Table
Table 1. Comparison Between Bubble and Membrane Oxygenator Groups
Age (years) Mean (SD)
Bubble
Membrane
Total = 264
Total = 236
58.4 (9.4)
58.5 (10.9)
Sex Men (%.) Women (%.)
188
(70)
78
(30)
Weight (kg) Mean (SD)
73.5 (12.6)
Height (cm) Mean (SD)
188.1 (10.6)
BSA (m*) Mean (SD)
1.8 (0.2)
161
(68)
75
(32)
71.7 (12.5) 167.4 (9.0) 1.8 (0.2)
NYHA No. of patients (%) Grade I Grade II
107
10
Grade III
100
Grade IV
47
(89)
14) (41)
10 106
(4) (45)
(38)
72
(31)
(18)
48
(20)
LV function No. of patients (%) Good Decreased
236
203
(86)
(9)
29
(12)
204
(77)
161
(68)
60
(23)
75
(32)
25
Operation-No. of patients (%) CABG Valve replacement Bypass time (min) Mean (SD)
71.9 (30.1)
78.2 (24.8)
Cross-clamp time (min) Mean (SD)
42.5 (15.6)
49.3 (19.8)
1). At each of maintained at a AaDO increased levels by 7 hours
the five sample times, the PaOz was supranormal level in both groups. The after bypass, but decreased to prebypass
postbypass (Fig 2). The mean prebypass AaDO* was 18.7 kPa (11.9) in the bubble group and 16.3 lcPa (9.9) in the membrane group. At each postbypass sample time, the increases in AaDO in the bubble and membrane groups were similar (Fig 2). When scored on two separate occasions both the EVLW score (repeatability coefficient = 5.16) and atelectasis score (repeatability coefficient = 0.94) showed reasonable repeatability. Fifty-two (98.1%) of the repeated EVLW scores were within two SD of the mean difference between the two scores. Although only 44 (83.1%) of the repeated atelectasis scores were within two SD of the mean difference between the two scores, 52 (98.1%) differed by less than one point. The EVLW scores (range O-41) and atelectasis scores (range O-4) increased postoperatively in both groups (Table 2). The EVLW water score peaked initially postoperatively then decreased. In contrast, the atelectasis score was
40
1 w
Change in AaDO &Pa)
Fig 2. Change in AaDO after cardiopulmonary bypass. Comparison of bubble and membrane groups. Mean (95% Cl).
100
200
300
Time (mins)
Bubble - 0 Membrane
REEVE, INGRAM, AND SMITH
504
Table 3. Change in Extravascular Lung Water and Atelectasis Scores After Cardiopulmonary
Bypass
_~....
Change in Atelectasis Score
Change in EVLW Score P value
P Value
Bubble
Membrane
Bubble
Membrane
Initial postoperative
2.91 (2.28-3.54)
2.06 (1.43-2.69)
10.01
1.06 (0.94-1.18)
0.86 (0.74-0.98)
co.01
First day postoperatively
1.65 (1 .OO-2.30)
1.07 (0.32-1.72)
1.68 (1.58-1.78)
1.55 (1.43-1.67)
NS
NOTE. Mean (95% Cl).
highest on the first postoperative day. Both groups showed the same trend. Postoperatively, the EVLW and atelectasis scores were higher in the bubble group than the membrane group. The increase in EVLW score (Table 3) was significantly greater in the bubble group than the membrane group for both the initial postoperative and the first day postoperative x-rays. The increase in the atelectasis score was significantly greater in the bubble group than the membrane group for the initial postoperative x-ray. There was no difference in outcome between bubble and membrane groups (Table 4). The hospital mortality was 10 (3.8%) patients in the bubble group and 10 (4.2%) patients in the membrane group. There was no significant difference in the following variables between bubble and membrane oxygenator groups: minimum hematocrit during bypass, minimum temperature during bypass, number of grafts, use of mammary artery grafts, perioperative fluid balance, time from end of bypass to intensive care unit (ICU) admission, use of inotropes, nitroprusside, intra-aortic balloon pump or PEEP within 7 hours postbypass or administration of diuretics within 24 hours postbypass. There was no correlation between either change in AaDO* or change in x-ray scores and age, height, weight, or body surface area. Change in AaDOz and change in x-ray scores were no different in patients with a history, signs, or pulmonary function tests suggestive of chronic respiratory disease than in patients with normal respiratory function preoperatively. The increase in the EVLW score was greater in the bubble group than the membrane group in both the coronary bypass and the valve surgery patients (Table 5). Similarly, the increase in atelectasis score was greater in the bubble group than the membrane group in both the coronary bypass and the valve surgery patients. However, these differences were not statistically significant. EVLW score was significantly greater in valve surgery patients than in coronary bypass patients, both preoperatively and postoperatively (Fig 3). In contrast, the postoperative atelectasis score was significantly greater in the coronary bypass Table 4. Duration of Artificial Ventilation, Survivors After Cardiopulmonary
ICU, and Hospital Stay in
Bypass: Comparison Between
patients than valve surgery patients. There was no difference in AaDOz between coronary bypass and valve surgery patients. There was no significant difference in change in AaDOz between bubble and membrane groups, divided according to operative procedure. In the initial period postbypass, increases in EVLW score, atelectasis score, and AaDOz were all significantly greater in men than women (Table 6). The increase in EVLW score was greater (P < 0.005) in NYHA Grade II or III patients than in Grade I patients (Fig 4). In NYHA Grade IV patients the preoperative EVLW score was already greater (P = 0.05) than in Grades I, II, and III and the perioperative increase was less. The prebypass AaDO was significantly greater in NYHA Grade IV patients, 20.3 kPa (12.9), than in Grade I patients, 14.5 kPa (11.7), (P < 0.05). There was no difference in change in AaDOz between NYHA grades. There was no difference in preoperative, postoperative, or change in atelectasis score between patients in different NYHA grades. The preoperative EVLW score in patients with decreased LV function was significantly greater than in patients with good LV function, (median 1.0 [interquartile range 0.0-4.01 v 0.0 [interquartile range 0.0-2.01, P < 0.01). However, there was no difference in change in EVLW score, atelectasis score, or AaDO between patients with good and patients with decreased LV function. The preoperative and postoperative EVLW scores were significantly greater in the patients with long bypass times (> 120 minutes) than in patients with shorter bypass times (Table 7). However, there was no difference in the change in x-ray scores between patients with long and short bypass times. In patients with short bypass times the increase in EVLW score was significantly greater in the bubble than
Table 5. Change in Extravascular Lung Water and Atelectasis Scores in Survivors After Cardiopulmonary
CABG Bubble
Membrane
Vsks Bubble
Membrane
Total = 201
Total = 157
Total = 53
Total = 69
3.19 (0.34)
2.56 (0.33)
2.04 (0.95)
1.25 (0.72)
1.62 (0.25)
1.36 (0.31)
1.35 (1.27)
0.80 (0.79)
1.15 (0.06) 0.96 (0.08)
0.64 (0.12)
0.64 (0.10)
1.75 (0.06)
1.46 (0.13)
1.38 (0.12)
Change in EVLW score Initial postoperative
Operative Procedures
Bypass: Comparison Between
Operative Procedures
First day postCABG Bubble
Valve
Membrane
Bubble
operatively
Membrane
Change in atelectasis
Total = 201
Total = 157
Total = 53
Total = 69
18.7 (17.7)
21.0 (35.6)
26.2 (29.2)
31.6 (56.7)
ICU stay (days)
1.5 (1.1)
1.5 (1.9)
2.1 (1.8)
2.2 (2.7)
First day post-
Hospital stay (days)
7.6 (2.1)
8.1 (5.8)
9.0 (4.0)
9.3 (5.1)
operatively
IPPV duration (hours)
NOTE. Mean (SD).
score Initial postoperative
NOTE. Mean (SEM)
1.64 (0.08)
OXYGENATORS
AND THE LUNGS
EVLW Score
Fig 3. Extravascular lung water (EVLW) and atelectesis scores after cardiopulmonary bypass. Comparison between operative procedures. Mean (95% Cl) ?? P < *P c 0.001. O-0, valve; 0.01. ?? m-m, CABG.
InitialPast-op 1s1Day post-op
Pre-op
the membrane group (Fig 5). Similarly, the AaDO was significantly greater in patients with long bypass times at all five time points. The change in AaDO* 90 minutes postbypass was significantly greater in patients with long bypass times than in those with short bypass times (22.9 kPa [SEM 3.51 v 13.1 kPa [SEM 0.71, P < O.Ol), but there was no difference between bubble and membrane groups. DISCUSSION The histologic changes in the lungs after cardiopulmo-
nary bypass are well documented and characterized by overwhelming engorgement of the pulmonary vascular bed, microatelectasis, and both interstitial and intraalveolar hemorrhage.20 Pulmonary dysfunction after cardiac surgery is multifactorial. Apart from the effects of cardiopulmonary bypass, other causes of dysfunction include inhibition of hypoxic pulmonary vasoconstriction by general anesthetics, reduction of ventilatory drive by opiates, decrease in surfactant production after bypass,21 preoperative lung disease, decrease in chest wall stability after sternotomy, decrease in blood supply to the intercostal muscles,22 or pleural effisionsz3 caused by internal mammary artery harvesting.22 In one study, 5 out of 52 patients had unequivocal phrenic nerve paresis postoperatively.24 Seventy-two percent of the patients have pleural effusions after cardiac surgery, especially if the cardiac index is less than 2.5 L/min/m2.2s Table 6. Change in Extravascular Lung Water Score, Atelectasis Score, and AaDO, After Cardiopulmonary
P&p
InitialPost-op 1st Day postop
Sixty-four percent of the patients have atelectasis, this being more frequent in patients with a positive fluid balance of over 4 L at the end of the operation.25 All of these factors can contribute to an increase in AaD02. In this study, there was an increase in intrapulmonary shunting, as measured by AaD02, after cardiopulmonary bypass in both groups (Fig 2). These increases are of similar magnitude to other studies of AaDO postbypass.5,26,27 Some studies of AaDO following bypass have shown a greater increase after bubble oxygenation than membrane oxygenation,5J0J7 especially in patients with long bypass times. However, these studies included fewer patients than in this study. Other studies, like this one, showed no difference in change in AaD024*s or shunt fractio@J8 between oxygenator types. Cardiopulmonary bypass causes increased microvascular permeability.28 Korsten et al investigated 32 patients undergoing cardiac surgery using a bubble oxygenator. Patients with an EVLW score greater than five 48 hours postoperatively had a higher AaD02, positive fluid balance, longer bypass times, and a lower thoracic electrical impedance than patients with a smaller EVLW score.27 (A low thoracic impedance signifies a high EVLW content.) EVLW, measured by the thermal indicator dilution technique, is increased on the day after bypass, but not 1 hour postoperatively. Although the colloid osmotic pressure during bypass was higher if plasma rather than Ringer’s was used in the prime, there was no difference between groups in colloid osmotic pressure or EVLW postoperatively.29 EVLW mea-
Bypass:
Comparison Between Sexes 6
Preoperative EVLW score
Male Total = 347
Female Total = 153
1.56 (0.19)
3.47 (0.54)
0.05
7I
PVdUe
6
Change in EVLW score Initial postoperative
2.96 (0.25)
1.45 (0.47)
First day postoperatively
1.70 (0.23)
0.64 (0.55)
NS
0.07 (0.02)
0.02 (0.01)
NS
1.05 (0.05)
0.75 (0.07)
0.002
Preoperative atelectasis score Change in atelectasis score Initial postoperative First day postoperatively Prebypass AaDO* (kPa)
Score
4 3 2
1.62 (0.05)
1.63 (0.07)
NS
17.06 (0.54)
16.69 (1.06)
NS
15.18 (0.83)
10.34 (1.47)
0.0001
14.06 (0.70)
9.99 (1.25)
0.0005
Change in AaDO? (kPa) 90 minutes postbypass
5 EVLW
1 0
Pre-op
Initial post-op
1st day post-op
Mean change in AaDO> postbypass NOTE. Mean (SEMI.
Fig 4. Extravascular lung water (EVLW) score after cardiopulmonary bypass. Comparison between New York Heart Association (NYHA) grades. Mean (95% Cl). ?? , I; 8, II; 0, Ill; ?,? IV.
REEVE,
506
Table 7. Extravascular Lung Water Score, Atelectasis Score, and AaDO
After Cardiopulmonary
Bypass: Comparison Between
Patients With Long Bypass Times and Those With Short Bypass Times BypassTime < 120
minutes
> 120
470
No. of Patients
minutes
P value
30
EVLW Score Preoperative
1.72
8.61 (1.68)
0.0002
Initial postoperative
4.35 (0.26)
8.00 (1.09)
0.003
First day postoperative
3.25 (0.24)
7.91 (1.17)
0.0007
Preoperative
0.05 (0.01)
0.03 (0.03)
NS
Initial postoperative
1 .Ol (0.04)
1.31 (0.19)
NS
First day postoperative
1.67 (0.04)
1.61 (0.16)
NS
(0.19)
Atelectasis score
AaDO, (kPa) Prebypass
17.26 (0.50)
22.49 (2.34)
0.04
20 minutes postbypass
47.87 (0.78)
54.84 (3.09)
0.04
90 minutes postbypass
30.37 (0.69)
46.28 (3.95)
0.0004
180 minutes postbypass
24.45 (0.71)
35.50 (3.57)
0.004
420 minutes postbypass
16.53 (0.51)
25.56 (3.91)
0.03
NOTE. Mean (SEM).
sured by double indicator dilution increased after bypass, peaking 45 minutes postbypass. This increase was less when 5 cmH20 PEEP was used during bypass. Several workers have investigated the effect of oxygenator type on markers of respiratory dysfunction. Kirklin et alI4 reported a significant relationship between high levels of C3a and postoperative pulmonary dysfunction. Nilsson et allo found greater release of the neutrophil granulocytic factors lactoferrin and myeloperoxidase after bubble oxygenation than membrane oxygenation but could find no relationship between activation of complement or granulocytes and pulmonary dysfunction. Byrick and Noble31 observed a significant rise in pulmonary vascular resistance immedi-
E --S_
1.
--__
--__ --__
-1
OJ Initial post-op
1 st day post op
Fig 5. Change in extravascular lung water (EVLW) score in patients with bypass times less than 120 minutes. Comparison between bubble and membrane groups. Mean (95% Cl). ?? P < 0.01. O-0, bubble; O-O, membrane.
INGRAM,
AND
SMlTb
ately postoperatively and an increase in lung water on the first and second postoperative days in patients in whom a bubble oxygenator was used. However, the mean absolute value for lung water was higher in the membrane group at all times. Although the chest x-ray cannot quantify lung water exactly, the severity of pulmonary edema seems better reflected by x-ray than the thermodilution measurement of lung water.“2 The thermodilution method overestimates the lung water volume compared to lung weight at postmortem by 10% to 15%. The chest x-ray film remains the reference standard against which other lung water content methods are compared. Its advantages include moderate accuracy, fair sensitivity, good reproducibility, noninvasiveness, practicality, availability, reliability, portability, ease of use in the emergency care setting, and relatively low cost. The x-ray score used in this study was validated by Pistolesi.” The score correlated well with EVLW measured by the indicator dilution method using radiolabelled albumin and tritiated water (r = 0.89, P < 0.001). The radiographic method was more sensitive than the indicator dilution method in earlier detection of interstitial edema, owing to its ability to detect regional edema at a stage when the increase in EVLW was still within the measurement error of the dilution technique.‘” The validity of the EVLW scoring in this study is supported by the repeatability coefficient, the increase in preoperative score with NYHA grade (Fig 4), and the association of higher score and decreased left ventricular function. The greater increase in EVLW and initial atelectasis scores (Table 3) seen in the bubble group may be due to increased microvascular permeability. It has been suggested that increased lung water contributes to atelectasis,25 which could explain the greater increase in initial postoperative atelectasis score. In most patients, the first day postoperative chest x-ray was taken postextubation (Table 4), hence other causes of atelectasis may well have masked any minor difference between the two oxygenator groups. The higher postoperative atelectasis score seen in the coronary bypass patients (Fig 3) may be attributed to dissection of mammary arteries. Although the range of EVLW scores was large, the distribution was skewed towards the lower range (Table 3), hence the small numerical change in scores represents a larger proportional change. Although the difference in x-ray scores between oxygenator groups found in this study appears to be a real difference, the clinical significance is small. Operative procedure (Table 5), sex (Table 6), and NYHA grade (Fig 4) are some of the other factors that appear to influence chest x-ray scores and AaD02. The greater change in lung scores and AaDO seen in men than women (Table 6) is difficult to explain. The incidence of high-risk patients33 and mortality34 has been found to be higher in women than men presenting for coronary surgery. This is consistent with the higher preoperative EVLW score in women in this study. Although artefact caused by breast shadows cannot be excluded, the atelectasis scores and AaDO changes would
OXYGENATORS
AND THE LUNGS
507
suggest that the difference between sexes in this study is not purely artefactual. It is interesting that the AaDO and EVLW scores were greater in patients with long bypass times, not only postbypass but also prebypass (Table 7). This suggests that the patients who subsequently have long bypass times are already a sicker group of patients preoperatively and that factors other than oxygenator type determine AaDO and EVLW. Patients with shorter bypass times are fitter than those with long bypass times, so the effect of different types of oxygenator is not masked by other factors (Fig 5). The duration of artificial ventilation, ICU stay and hospital stay varied with operative procedure, but not with oxygenator group (Table 4). However,,these outcome measures are also influenced by postoperative management protocols, not just by clinical state. Other
studies4J1 also found no difference in duration of ventilation between oxygenator groups. Although there was a significantly greater increase in extravascular lung water score and atelectasis score in the bubble group compared to the membrane group, there was no evidence that either intrapulmonary shunting or clinical outcome were influenced by the type of oxygenator during bypass.
ACKNOWLEDGMENT
We are grateful for the help of the senior perfusionist, Margaret Russell, and her staff, Gordon Murray for help with statistics, and to, all cardiac surgeons and anesthetists at the Western Infirmary, Glasgow, who cooperated with the study.
REFERENCES
1. Blauth CI, Smith Pl, Arnold JV, et al: Influence of oxygenator type on the prevalence and extent of microembolic retinal ischaemia during cardiopulmonary bypass. J Thorac Cardiovasc Surg 99:61-9, 1990 2. Deverall PB, Padayachee TS, Parsons S, et al: Ultrasound detection of micro-emboli in the middle cerebral artery during cardiopulmonary bypass surgery. Eur J Cardiothorac Surg 2:256260,1988 3. Van Oeveren W, Kazatchkine MD, Descamps-Latscha B, et al: Deleterious effects of cardiopulmonary bypass: A prospective study of bubble versus membrane oxygenation. J Thorac Cardiovascular Surg 89:888-889,1985 4. Hessel II EA, Johnson DD, Ivey TD, et al: Membrane versus bubble oxygenator for cardiac operations: A prospective randomized study. J Thorac Cardiovasc Surg 80:111-122,198O 5. Dhumale R, Lake S, Pepper J: A prospective comparison of bubble and membrane oxygenators in short and long perfusions. Eur J Cardiothorac Surg 1:20-22,1987 6. Hakoshima A, Goto H, Abe K, et al: Alteration of red cell deformability during extracorporeal bypass: Membrane v bubble oxygenator. J Cardiothorac Anesth 3:189-192,1989 7. Boonstra PW, Vermeulen FE, Leusink JA, et al: Hematological advantage of a membrane oxygenator over a bubble oxygenator in long perfusions. Ann Thorac Surg 41:297-300,1986 8. van den Dungen JJAM, Karliczek GF, Brenken I-l, et al: Clinical study of blood trauma during perfusion with membrane and bubble oxygenators. J Thorac Cardiovasc Surg 83:108-116, 1982 9. Teoh KH, Christakis GT, Weisel RD, et al: Blood conservation with membrane oxygenators and dipyridamole. Ann Thorac Surg 44:40-47,1987 10. Nilsson L, Tyden H, Johansson 0, et al: Bubble and membrane oxygenators: Comparison of postoperative organ dysfunction with special reference to inflammatory activity. Stand J Thor Cardiovasc Surg 24:59-64,199O 11. Cavorocchi NC, Pluth JR, Schaff HV, et al: Complement activation during cardiopulmonary bypass. J Cardiovasc Surg 91:252-258,1986 12. Nilsson L, Nilsson U, Venge P, et al: Inflammatory system activation during cardiopulmonary bypass as an indicator of biocompatability: a randomized comparison of bubble and membrane oxygenators. Stand J Thor Cardiovasc Surg 24:53-58,199O 13. Gu YJ, Wang YS, Chiang BY, et al: Membrane oxygenator prevents lung reperfusion injury in canine cardiopulmonary bypass. Ann Thorac Surg 51:573-578,199l
14. Kirklin JK, Westaby S, Blackstone EH, et al: Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovascular Surg 86:845-857,1983 15. Wachtfogel YT, Kucich U, Greenplate J, et al: Human neutrophil degranulation during extracorporeal circulation. Blood 69,1:324-330,1987 16. Boldt J, von Bormann B, Kling D, et al: New membrane oxygenator (LPM 50): Influence on extravascular lung water and pulmonary function in comparison to bubble oxygenator. J Thorac Cardiovasc Surg 92:798-800,1986 17. Biagioli B, Rossi C, Giomarelli PP, et al: Correlations between membrane and bubble oxygenators in patients treated with or without methylprednisolone. Haemodynamic and metabolic parameters. G Ital Cardiol11:1288-1300,198l 18. Sade RM, Bartles DM, Dearing JP, et al: A prospective randomized study of membrane versus bubble oxygenators in children. Ann Thorac Surg 29,6:502-511,198O 19. Pistolesi M, Giuntini C: Assessment of extravascular lung water. Radio1 Clin N Am 16:551-574,1978 20. Wilson J: The pulmonary cellular and subcellular alterations of extracorporeal circulation. Surg Clin N Am 54:1203-1220,1974 21. Asada S, Yamaguchi M: Fine structural change in the lung following cardiopulmonary bypass. Chest 59:478-483,1979 22. Berrizbeitia LD, Tessler S, Jacobowitz L, et al: Effect of sternotomy and coronary bypass surgery on postoperative pulmonary mechanics: Comparison of internal mammary and saphenous vein bypass grafts. Chest 96:873-876,1989 23. Kollef MH, Peller T, Knodel A, et al: Delayed pleuropulmonary complications following coronary revascularization with the internal mammary artery. Chest 94:68-71,1988 24. Wilcox P, Baile EM, Hards J, et al: Phrenic nerve function and its relationship to atelectasis after coronary artery bypass surgery. Chest 93:693-698,1988 25. Gale GD, Teasdale SJ, Sanders DE, et al: Pulmonary atelectasis and other respiratory complications after cardiopulmonary bypass and investigation of aetiological factors. Canad Anaesth Sot J 26:15-21,1979 26. Andersen NB, Ghia J: Pulmonary function, cardiac status and postoperative course in relation to cardiopulmonary bypass. J Thorac Cardiovasc Surg 59:474-483,197O 27. Korsten HHM, Leusink JA, Spierdijk J, et al: Pulmonary shunting after cardiopulmonary bypass. Eur Heart J 10:17-21,1989 28. Smith EEJ, Naftel DC, Kirklin JW: Microvascular permeability after cardiopulmonary bypass: An experimental study. J Thorac Cardiovasc Surg 94:225-233,1987
REEVE, INGRAM,
29. Byrick RJ, Kay JC, Noble WH: Extravascular lung water accumulation in patients following coronary artery surgery. Canad Anaesth Sot J 24:332-345,1977 30. Boldt J, Kling D, Scheld HH, Hempelmann G: Lung management during cardiopulmonary bypass: Influence on extravascular lung water. J Cardiothorac Anesth 4:73-79,199O 31. Byrick RJ, Noble WH: Postperfusion lung syndrome. Comparison of Travenol bubble and membrane oxygenators. J Thorac Cardiovasc Surg 76:685-693,1978
AND SMITH
32. Pistolesi M, Miniati M, Giuntini C: A radiographic score toiclinical use in the adult respiratory distress syndrome. Int Crit Care Digest 7:2-4. 1988 33. Tremblay NA, Hardy J, Perrault J, Carrier M: A simple classification of risk in cardiac surgery: The first decade. Can J Anaesth 40:103-111,1993 34. Khan SS, Nessim S, Gray R, et al: Increased mortality of women in coronary bypass surgery: Evidence for referral bias. Ann Intern Med 112:561-567, 1990
T
HERE ARE several consequences of cardiopulmonary bypass that may be more common when a bubble oxygenator is used than when a membrane oxygenator is used. These include microembolic retinal ischemia,1,2 damage to erythrocytes and platelets,3-7 with consequent bleeding and transfusion requirement, 8,yincrease in serum creatinine,lO requirement for inotropic support,lO complement activation,” activation of neutrophil granulocytes,3J0J2 transpulmonary sequestration of leukocytes,“J” and postbypass neutropenia.” Complement activation increases lung endothelial permeability14 causing pulmonary dysfunction. Neutrophil activation may also contribute to pulmonary dysfunction.3J3,15 Lung leukocyte and platelet sequestration and extravascular lung water are increased after bubble oxygenation in dog lungs,” but in a study of 30 patients there was no difference in EVLW measured by the double indicator dilution method between oxygenator types.16 Previous studies comparing the influence of oxygenator type on intrapulmonary shunt have given differing results,4,5J0J6-18so the clinical importance of any difference between oxygenator types is not known. The aim of this study was to determine whether there is a clinical difference in respiratory function between patients in whom a bubble oxygenator is used during bypass and patients in whom a membrane oxygenator is used. PATIENTS AND METHODS A consecutive sample of 500 adults undergoing cardiac surgery requiring cardiopulmonary bypass was studied after ethical committee approval was obtained. Exclusion criteria were (1) patients with intracardiac shunting and (2) whether the surgeon or anesthesiologist preferred to use a particular oxygenator for clinical reasons. Patients were randomly allocated to cardiopulmonary bypass
From Western Infirmary, Glasgow, Scotland. Address reprint requests to W G. Reeve, FRCA, Consultant Anaesthe&, Division of Anaesthesia, Royal Infirma y, Glasgow, G3I ZER, Scotland. Copyright 0 1994 by W.B. Saunders Company 1053-0770/9410805-0004$03.00/O
502
score was significantly greater in the bubble group (mean 1.08,95% Cl 0.94-1.18) than the membrane group (mean 0.86, 95% Cl 0.74-0.98) for the initial postoperative
x-rays (P c 0.01)
but not for the x-rays on the first postoperative was no difference
in duration of ventilation,
day. There
intensive care,
hospital stay, or hospital mortality between bubble and membrane groups. Although there was a statistically significant difference in x-ray scores between neither intrapulmonary
shunting
oxygenator
groups,
nor clinical outcome
influenced by the type of oxygenator
was
used during bypass.
Copyright 8 1994 by W.B. Saunders Company KEY WORDS: respiratory function, cardiopulmonary
bypass,
oxygenator
with either a Bard bubble oxygenator H1700 (bubble group) or a Bard hollow fiber membrane oxygenator HF5700 (membrane group). Bypass management was otherwise identical in both groups. The bypass circuit was primed with two liters of Hartmann’s solution to which was added 10 g of mannitol and 50 mmol of sodium bicarbonate. The flow index was 2.4 L/minim2 at 37°C reducing to 1.8 L/minim2 at 26 to 28°C. Alpha-stat acid-base control was used, and CO2 was added to the gas flow in the bubble oxygenator group. The first of the main outcome measures was alveolar-arterial oxygen tension gradient (AaDO?). Arterial blood gases were taken prebypass then 20, 90, 180, and 420 minutes postbypass. The fractional inspired oxygen concentration (F102) was also measured using a calibrated fuel cell. The alveolar partial pressure of oxygen (PA02) was calculated using the following equation: PA02
PaC02 = P102 - 7
1-R
+
I
PaC02.
FIOz.
-g-I
where P,Oz = inspired partial pressure of oxygen, PaC02 = arterial partial pressure of carbon dioxide, and R = respiratory exchange ratio, assumed to be 0.82. For each time point AaDO was calculated. The magnitude of this gradient is proportional to the intrapulmonary shunt. Other outcome measures were extravascular lungwater (EVLW) and atelectasis scores. Preoperative, initial postoperative, and first day postoperative chest x-rays were reviewed by a radiologist blinded to the type of oxygenator used. Each x-ray was assigned an EVLW scorei and an atelectasis score (Fig 1). Repeatability of the EVLW and atelectasis scores was assessed on a random sample of 53 of the x-rays used in the study. Additional outcome measures were duration of postoperative artificial ventilation, duration of stay in intensive care (ICU). and hospital outcome. The final outcome data were other perioperative factors that could have influenced postoperative respiratory function, which were obtained from the patients notes. These included a preoperative history of respiratory disease, pulmonary function tests, smoking history, New York Heart Association (NYHA) classification, left ventricular (LV) function, medication, operative procedure, bypass and aortic cross-clamp times, minimum patient temperature during bypass, and postoperative fluid balance. Decreased LV function was defined as a preoperative LVEDP greater than 18 mmHg or an ejection fraction less than 30%. Statistical analysis was performed using the Minitab 7 statistics package (Minitab Inc). Statistical tests included the unpaired
Journalof Cardiothoracic and VascularAnesthesia,
Vol8,
No 5 (October),
1994: pp 502.508
OXYGENATORS
AND THE LUNGS
503
Table 2. Perioperative Extravascular Lung Water
ScorC
Chest X-ray finding
mild
and Atelectasis Scores
c
EVLW Score
marked
Atelectasis confined to one quadrant
0.5
1.0
Atelectssis in two quadrants
1.0
2.0
Initial
Atelectasis in three qua&ants
1.5
3.0
First Day
Atelectasis in all four quadrants
2.0
4.0
Preoperative postoperative Postoperative
Atelectasis
Score
Bubble
Membrane
Bubble
Membrane
0.0 (0.0-2.0)
0.0 (0.0-3.0)
0.0 (0.0-0.0)
0.0 (0.0-0.0)
3.5 (11.0-7.0) 3.0 (0.0-7.0)
1.0 (0.0-2.0)
1.0 (0.0-2.0)
2.0 (0.0-5.0)
2.0 (1 .O-2.0) 2.0 (1 .O-2.0)
1 .O (0.0-4.0)
NOTE. Median (interquartile range).
Mann-Whitney U test, x2 test, Spearman rank correlation and Kruskal-Wallis as appropriate. Results are quoted as mean (*SD) unless otherwise stated.
t-test, Fig 1.
Atelectasis scoring system.
RESULTS
Three hundred sixty-five (73%) coronary bypass procedures and 135 (27%) valve replacements were studied. The two groups were comparable for age, sex, height, weight, body surface area, NYHA grade, and LV function (Table
Table 1. Comparison Between Bubble and Membrane Oxygenator Groups
Age (years) Mean (SD)
Bubble
Membrane
Total = 264
Total = 236
58.4 (9.4)
58.5 (10.9)
Sex Men (%.) Women (%.)
188
(70)
78
(30)
Weight (kg) Mean (SD)
73.5 (12.6)
Height (cm) Mean (SD)
188.1 (10.6)
BSA (m*) Mean (SD)
1.8 (0.2)
161
(68)
75
(32)
71.7 (12.5) 167.4 (9.0) 1.8 (0.2)
NYHA No. of patients (%) Grade I Grade II
107
10
Grade III
100
Grade IV
47
(89)
14) (41)
10 106
(4) (45)
(38)
72
(31)
(18)
48
(20)
LV function No. of patients (%) Good Decreased
236
203
(86)
(9)
29
(12)
204
(77)
161
(68)
60
(23)
75
(32)
25
Operation-No. of patients (%) CABG Valve replacement Bypass time (min) Mean (SD)
71.9 (30.1)
78.2 (24.8)
Cross-clamp time (min) Mean (SD)
42.5 (15.6)
49.3 (19.8)
1). At each of maintained at a AaDO increased levels by 7 hours
the five sample times, the PaOz was supranormal level in both groups. The after bypass, but decreased to prebypass
postbypass (Fig 2). The mean prebypass AaDO* was 18.7 kPa (11.9) in the bubble group and 16.3 lcPa (9.9) in the membrane group. At each postbypass sample time, the increases in AaDO in the bubble and membrane groups were similar (Fig 2). When scored on two separate occasions both the EVLW score (repeatability coefficient = 5.16) and atelectasis score (repeatability coefficient = 0.94) showed reasonable repeatability. Fifty-two (98.1%) of the repeated EVLW scores were within two SD of the mean difference between the two scores. Although only 44 (83.1%) of the repeated atelectasis scores were within two SD of the mean difference between the two scores, 52 (98.1%) differed by less than one point. The EVLW scores (range O-41) and atelectasis scores (range O-4) increased postoperatively in both groups (Table 2). The EVLW water score peaked initially postoperatively then decreased. In contrast, the atelectasis score was
40
1 w
Change in AaDO &Pa)
Fig 2. Change in AaDO after cardiopulmonary bypass. Comparison of bubble and membrane groups. Mean (95% Cl).
100
200
300
Time (mins)
Bubble - 0 Membrane
REEVE, INGRAM, AND SMITH
504
Table 3. Change in Extravascular Lung Water and Atelectasis Scores After Cardiopulmonary
Bypass
_~....
Change in Atelectasis Score
Change in EVLW Score P value
P Value
Bubble
Membrane
Bubble
Membrane
Initial postoperative
2.91 (2.28-3.54)
2.06 (1.43-2.69)
10.01
1.06 (0.94-1.18)
0.86 (0.74-0.98)
co.01
First day postoperatively
1.65 (1 .OO-2.30)
1.07 (0.32-1.72)
1.68 (1.58-1.78)
1.55 (1.43-1.67)
NS
NOTE. Mean (95% Cl).
highest on the first postoperative day. Both groups showed the same trend. Postoperatively, the EVLW and atelectasis scores were higher in the bubble group than the membrane group. The increase in EVLW score (Table 3) was significantly greater in the bubble group than the membrane group for both the initial postoperative and the first day postoperative x-rays. The increase in the atelectasis score was significantly greater in the bubble group than the membrane group for the initial postoperative x-ray. There was no difference in outcome between bubble and membrane groups (Table 4). The hospital mortality was 10 (3.8%) patients in the bubble group and 10 (4.2%) patients in the membrane group. There was no significant difference in the following variables between bubble and membrane oxygenator groups: minimum hematocrit during bypass, minimum temperature during bypass, number of grafts, use of mammary artery grafts, perioperative fluid balance, time from end of bypass to intensive care unit (ICU) admission, use of inotropes, nitroprusside, intra-aortic balloon pump or PEEP within 7 hours postbypass or administration of diuretics within 24 hours postbypass. There was no correlation between either change in AaDO* or change in x-ray scores and age, height, weight, or body surface area. Change in AaDOz and change in x-ray scores were no different in patients with a history, signs, or pulmonary function tests suggestive of chronic respiratory disease than in patients with normal respiratory function preoperatively. The increase in the EVLW score was greater in the bubble group than the membrane group in both the coronary bypass and the valve surgery patients (Table 5). Similarly, the increase in atelectasis score was greater in the bubble group than the membrane group in both the coronary bypass and the valve surgery patients. However, these differences were not statistically significant. EVLW score was significantly greater in valve surgery patients than in coronary bypass patients, both preoperatively and postoperatively (Fig 3). In contrast, the postoperative atelectasis score was significantly greater in the coronary bypass Table 4. Duration of Artificial Ventilation, Survivors After Cardiopulmonary
ICU, and Hospital Stay in
Bypass: Comparison Between
patients than valve surgery patients. There was no difference in AaDOz between coronary bypass and valve surgery patients. There was no significant difference in change in AaDOz between bubble and membrane groups, divided according to operative procedure. In the initial period postbypass, increases in EVLW score, atelectasis score, and AaDOz were all significantly greater in men than women (Table 6). The increase in EVLW score was greater (P < 0.005) in NYHA Grade II or III patients than in Grade I patients (Fig 4). In NYHA Grade IV patients the preoperative EVLW score was already greater (P = 0.05) than in Grades I, II, and III and the perioperative increase was less. The prebypass AaDO was significantly greater in NYHA Grade IV patients, 20.3 kPa (12.9), than in Grade I patients, 14.5 kPa (11.7), (P < 0.05). There was no difference in change in AaDOz between NYHA grades. There was no difference in preoperative, postoperative, or change in atelectasis score between patients in different NYHA grades. The preoperative EVLW score in patients with decreased LV function was significantly greater than in patients with good LV function, (median 1.0 [interquartile range 0.0-4.01 v 0.0 [interquartile range 0.0-2.01, P < 0.01). However, there was no difference in change in EVLW score, atelectasis score, or AaDO between patients with good and patients with decreased LV function. The preoperative and postoperative EVLW scores were significantly greater in the patients with long bypass times (> 120 minutes) than in patients with shorter bypass times (Table 7). However, there was no difference in the change in x-ray scores between patients with long and short bypass times. In patients with short bypass times the increase in EVLW score was significantly greater in the bubble than
Table 5. Change in Extravascular Lung Water and Atelectasis Scores in Survivors After Cardiopulmonary
CABG Bubble
Membrane
Vsks Bubble
Membrane
Total = 201
Total = 157
Total = 53
Total = 69
3.19 (0.34)
2.56 (0.33)
2.04 (0.95)
1.25 (0.72)
1.62 (0.25)
1.36 (0.31)
1.35 (1.27)
0.80 (0.79)
1.15 (0.06) 0.96 (0.08)
0.64 (0.12)
0.64 (0.10)
1.75 (0.06)
1.46 (0.13)
1.38 (0.12)
Change in EVLW score Initial postoperative
Operative Procedures
Bypass: Comparison Between
Operative Procedures
First day postCABG Bubble
Valve
Membrane
Bubble
operatively
Membrane
Change in atelectasis
Total = 201
Total = 157
Total = 53
Total = 69
18.7 (17.7)
21.0 (35.6)
26.2 (29.2)
31.6 (56.7)
ICU stay (days)
1.5 (1.1)
1.5 (1.9)
2.1 (1.8)
2.2 (2.7)
First day post-
Hospital stay (days)
7.6 (2.1)
8.1 (5.8)
9.0 (4.0)
9.3 (5.1)
operatively
IPPV duration (hours)
NOTE. Mean (SD).
score Initial postoperative
NOTE. Mean (SEM)
1.64 (0.08)
OXYGENATORS
AND THE LUNGS
EVLW Score
Fig 3. Extravascular lung water (EVLW) and atelectesis scores after cardiopulmonary bypass. Comparison between operative procedures. Mean (95% Cl) ?? P < *P c 0.001. O-0, valve; 0.01. ?? m-m, CABG.
InitialPast-op 1s1Day post-op
Pre-op
the membrane group (Fig 5). Similarly, the AaDO was significantly greater in patients with long bypass times at all five time points. The change in AaDO* 90 minutes postbypass was significantly greater in patients with long bypass times than in those with short bypass times (22.9 kPa [SEM 3.51 v 13.1 kPa [SEM 0.71, P < O.Ol), but there was no difference between bubble and membrane groups. DISCUSSION The histologic changes in the lungs after cardiopulmo-
nary bypass are well documented and characterized by overwhelming engorgement of the pulmonary vascular bed, microatelectasis, and both interstitial and intraalveolar hemorrhage.20 Pulmonary dysfunction after cardiac surgery is multifactorial. Apart from the effects of cardiopulmonary bypass, other causes of dysfunction include inhibition of hypoxic pulmonary vasoconstriction by general anesthetics, reduction of ventilatory drive by opiates, decrease in surfactant production after bypass,21 preoperative lung disease, decrease in chest wall stability after sternotomy, decrease in blood supply to the intercostal muscles,22 or pleural effisionsz3 caused by internal mammary artery harvesting.22 In one study, 5 out of 52 patients had unequivocal phrenic nerve paresis postoperatively.24 Seventy-two percent of the patients have pleural effusions after cardiac surgery, especially if the cardiac index is less than 2.5 L/min/m2.2s Table 6. Change in Extravascular Lung Water Score, Atelectasis Score, and AaDO, After Cardiopulmonary
P&p
InitialPost-op 1st Day postop
Sixty-four percent of the patients have atelectasis, this being more frequent in patients with a positive fluid balance of over 4 L at the end of the operation.25 All of these factors can contribute to an increase in AaD02. In this study, there was an increase in intrapulmonary shunting, as measured by AaD02, after cardiopulmonary bypass in both groups (Fig 2). These increases are of similar magnitude to other studies of AaDO postbypass.5,26,27 Some studies of AaDO following bypass have shown a greater increase after bubble oxygenation than membrane oxygenation,5J0J7 especially in patients with long bypass times. However, these studies included fewer patients than in this study. Other studies, like this one, showed no difference in change in AaD024*s or shunt fractio@J8 between oxygenator types. Cardiopulmonary bypass causes increased microvascular permeability.28 Korsten et al investigated 32 patients undergoing cardiac surgery using a bubble oxygenator. Patients with an EVLW score greater than five 48 hours postoperatively had a higher AaD02, positive fluid balance, longer bypass times, and a lower thoracic electrical impedance than patients with a smaller EVLW score.27 (A low thoracic impedance signifies a high EVLW content.) EVLW, measured by the thermal indicator dilution technique, is increased on the day after bypass, but not 1 hour postoperatively. Although the colloid osmotic pressure during bypass was higher if plasma rather than Ringer’s was used in the prime, there was no difference between groups in colloid osmotic pressure or EVLW postoperatively.29 EVLW mea-
Bypass:
Comparison Between Sexes 6
Preoperative EVLW score
Male Total = 347
Female Total = 153
1.56 (0.19)
3.47 (0.54)
0.05
7I
PVdUe
6
Change in EVLW score Initial postoperative
2.96 (0.25)
1.45 (0.47)
First day postoperatively
1.70 (0.23)
0.64 (0.55)
NS
0.07 (0.02)
0.02 (0.01)
NS
1.05 (0.05)
0.75 (0.07)
0.002
Preoperative atelectasis score Change in atelectasis score Initial postoperative First day postoperatively Prebypass AaDO* (kPa)
Score
4 3 2
1.62 (0.05)
1.63 (0.07)
NS
17.06 (0.54)
16.69 (1.06)
NS
15.18 (0.83)
10.34 (1.47)
0.0001
14.06 (0.70)
9.99 (1.25)
0.0005
Change in AaDO? (kPa) 90 minutes postbypass
5 EVLW
1 0
Pre-op
Initial post-op
1st day post-op
Mean change in AaDO> postbypass NOTE. Mean (SEMI.
Fig 4. Extravascular lung water (EVLW) score after cardiopulmonary bypass. Comparison between New York Heart Association (NYHA) grades. Mean (95% Cl). ?? , I; 8, II; 0, Ill; ?,? IV.
REEVE,
506
Table 7. Extravascular Lung Water Score, Atelectasis Score, and AaDO
After Cardiopulmonary
Bypass: Comparison Between
Patients With Long Bypass Times and Those With Short Bypass Times BypassTime < 120
minutes
> 120
470
No. of Patients
minutes
P value
30
EVLW Score Preoperative
1.72
8.61 (1.68)
0.0002
Initial postoperative
4.35 (0.26)
8.00 (1.09)
0.003
First day postoperative
3.25 (0.24)
7.91 (1.17)
0.0007
Preoperative
0.05 (0.01)
0.03 (0.03)
NS
Initial postoperative
1 .Ol (0.04)
1.31 (0.19)
NS
First day postoperative
1.67 (0.04)
1.61 (0.16)
NS
(0.19)
Atelectasis score
AaDO, (kPa) Prebypass
17.26 (0.50)
22.49 (2.34)
0.04
20 minutes postbypass
47.87 (0.78)
54.84 (3.09)
0.04
90 minutes postbypass
30.37 (0.69)
46.28 (3.95)
0.0004
180 minutes postbypass
24.45 (0.71)
35.50 (3.57)
0.004
420 minutes postbypass
16.53 (0.51)
25.56 (3.91)
0.03
NOTE. Mean (SEM).
sured by double indicator dilution increased after bypass, peaking 45 minutes postbypass. This increase was less when 5 cmH20 PEEP was used during bypass. Several workers have investigated the effect of oxygenator type on markers of respiratory dysfunction. Kirklin et alI4 reported a significant relationship between high levels of C3a and postoperative pulmonary dysfunction. Nilsson et allo found greater release of the neutrophil granulocytic factors lactoferrin and myeloperoxidase after bubble oxygenation than membrane oxygenation but could find no relationship between activation of complement or granulocytes and pulmonary dysfunction. Byrick and Noble31 observed a significant rise in pulmonary vascular resistance immedi-
E --S_
1.
--__
--__ --__
-1
OJ Initial post-op
1 st day post op
Fig 5. Change in extravascular lung water (EVLW) score in patients with bypass times less than 120 minutes. Comparison between bubble and membrane groups. Mean (95% Cl). ?? P < 0.01. O-0, bubble; O-O, membrane.
INGRAM,
AND
SMlTb
ately postoperatively and an increase in lung water on the first and second postoperative days in patients in whom a bubble oxygenator was used. However, the mean absolute value for lung water was higher in the membrane group at all times. Although the chest x-ray cannot quantify lung water exactly, the severity of pulmonary edema seems better reflected by x-ray than the thermodilution measurement of lung water.“2 The thermodilution method overestimates the lung water volume compared to lung weight at postmortem by 10% to 15%. The chest x-ray film remains the reference standard against which other lung water content methods are compared. Its advantages include moderate accuracy, fair sensitivity, good reproducibility, noninvasiveness, practicality, availability, reliability, portability, ease of use in the emergency care setting, and relatively low cost. The x-ray score used in this study was validated by Pistolesi.” The score correlated well with EVLW measured by the indicator dilution method using radiolabelled albumin and tritiated water (r = 0.89, P < 0.001). The radiographic method was more sensitive than the indicator dilution method in earlier detection of interstitial edema, owing to its ability to detect regional edema at a stage when the increase in EVLW was still within the measurement error of the dilution technique.‘” The validity of the EVLW scoring in this study is supported by the repeatability coefficient, the increase in preoperative score with NYHA grade (Fig 4), and the association of higher score and decreased left ventricular function. The greater increase in EVLW and initial atelectasis scores (Table 3) seen in the bubble group may be due to increased microvascular permeability. It has been suggested that increased lung water contributes to atelectasis,25 which could explain the greater increase in initial postoperative atelectasis score. In most patients, the first day postoperative chest x-ray was taken postextubation (Table 4), hence other causes of atelectasis may well have masked any minor difference between the two oxygenator groups. The higher postoperative atelectasis score seen in the coronary bypass patients (Fig 3) may be attributed to dissection of mammary arteries. Although the range of EVLW scores was large, the distribution was skewed towards the lower range (Table 3), hence the small numerical change in scores represents a larger proportional change. Although the difference in x-ray scores between oxygenator groups found in this study appears to be a real difference, the clinical significance is small. Operative procedure (Table 5), sex (Table 6), and NYHA grade (Fig 4) are some of the other factors that appear to influence chest x-ray scores and AaD02. The greater change in lung scores and AaDO seen in men than women (Table 6) is difficult to explain. The incidence of high-risk patients33 and mortality34 has been found to be higher in women than men presenting for coronary surgery. This is consistent with the higher preoperative EVLW score in women in this study. Although artefact caused by breast shadows cannot be excluded, the atelectasis scores and AaDO changes would
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suggest that the difference between sexes in this study is not purely artefactual. It is interesting that the AaDO and EVLW scores were greater in patients with long bypass times, not only postbypass but also prebypass (Table 7). This suggests that the patients who subsequently have long bypass times are already a sicker group of patients preoperatively and that factors other than oxygenator type determine AaDO and EVLW. Patients with shorter bypass times are fitter than those with long bypass times, so the effect of different types of oxygenator is not masked by other factors (Fig 5). The duration of artificial ventilation, ICU stay and hospital stay varied with operative procedure, but not with oxygenator group (Table 4). However,,these outcome measures are also influenced by postoperative management protocols, not just by clinical state. Other
studies4J1 also found no difference in duration of ventilation between oxygenator groups. Although there was a significantly greater increase in extravascular lung water score and atelectasis score in the bubble group compared to the membrane group, there was no evidence that either intrapulmonary shunting or clinical outcome were influenced by the type of oxygenator during bypass.
ACKNOWLEDGMENT
We are grateful for the help of the senior perfusionist, Margaret Russell, and her staff, Gordon Murray for help with statistics, and to, all cardiac surgeons and anesthetists at the Western Infirmary, Glasgow, who cooperated with the study.
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