Changes of Pulmonary Function Following Transfusion of Stored Blood M. T A K A O RN. I , NAKAJO,A N D T. I S H I I From the Deparrment of Anesthesiology. Kawasaki Universirv. School of Medicine. O k a y m a . Japan
Ventilatory volumes, blood gnses and other aspects of pulmonary function were measured before and after intraoperative transfusion in 16 patients who had undergone operation under general anesthesia. One group consisted o f eight patients transfused w i t h 1275 m l o f stored blood passed through a standard nylon mesh filter (SF group) and the other consisted o f eight patients transfused with stored blood passed through a dacron wool filter (DWF group). Since respiration o f the patients was depressed slightly due to preanesthetic sedation, lowered VE. VT, and el+ vated Paco2,respiratory dead space ratio VD/VT were observed either in the SF or DWF group before anesthesia and transfusion. Even after the recovery o f patients from an~ ~ in ~ the thesia VD/VT remained high and F E decreased SF group. In contrast, VD/VT decreased almost to normal ~ ~ normal ~ in the D W F group. Fraction and F E remained o f physiological shunt Qs/Qt tended to decrease after anesthesia and transfusion either i n the SF or D W F group. The ventilation-perfusion ratio increased relatively more markedly and pHa elevated definitely in the S F group after transfusion. The above data indicate that microembolism occurs after transfusion ofstored blood. even in an amount o f 1.000 ml, with a standard nylon mesh filter and concealed pulmonary dysfunction is observable. Therefore, a fine filter, such as a dacron wool filter or a polyester mesh filter, is r e c o m mended to avoid the pulmonary microembolism and the consequent respiratory distress following the transfusion o f stared blood.
.SWANK indicated that the pulmonary dysfunction following massive blood transfusion could be caused by diffuse pulmonary microembolism.Ig Microemboli were demonstrated microscopically in the lungs of patients who were given large volumes of stored blood.I2 Cornell and Swank.' reported that massive transfusion of stored blood could cause the diffuse microembolism in lungs of dogs experimentally. Reul'" reported that pulmonary arterioles of the lungs in patients who were Received for publication August 23, 1976: accepted November 20, 1976.
transfused with 10 to 63 units of stored blood were filled with fragmented platelets and leukocytes. MoselyI5 reported a patient who died from respiratory insufficiency associated with multiple pulmonary emboli following massive transfusion. Therefore, it has been recommended that a finer mesh filter must be used for prevention of the subsequent respiratory distress. Several experiments have been done to study changes of pulmonary function due to diffuse microembolism in anim a1s."!'. N o study along this line has been done in humans. This study was designed to observe changes of pulmonary function following intraoperative transfusion of stored blood and to evaluate the efficacy of a dacron wool filter for avoiding the respiratory distress after transfusion. Methods
The subjects were 16 patients who had major surgery under general anesthesia and received more than 1,000 mi of blood intrnoperatively. They showed no abnormality in their pulmonary function preoperatively. They were divided at random into two groups. Eight patients received stored ACD blood through standard transfusion sets with nylon mesh filters (SF group). The other eight patients received stored ACD blood through transfusion sets with dacron wool filters (DWF group). The average age of the patients in the SF group was 5 I years and the average age of patients in the DWF group was 44 years. Except for a mastectomy and an amputation of a lower extremity in patients of the SF group all were abdominal operations. Patients of the SF group received from 1,000 to 1,800 m l of blood (average use: 1,275 ml) while the DWF group received from 1,000 to 2,800 ml of blood (average use: 1,375 rnl). All of the patients received 0.5 mg o f atropine
615 Trnnrlurion Nov.-l)ec. 1977
Vulunic 17
Numhcrh
616
Transfusion
TAKORI ET AL
and 15 mg of pentazocine subcutaneously one hour before anesthesia. In addition, 7.5 mg of droperidol and 10 mg of diazepam were given intravenously ten minutes before endotracheal intubation. Topical anesthesia with 2 per cent of lidocaine was done on the oral, pharyngeal, and intratracheal surface and then a cuffed endotracheal tube was intubated. The patient was left to breathe room air spontaneously through a nonrebreathing valve, the expiratory orifice of which was connected to a Douglas bag with a short rubber tube if necessary to collect expiratory gas. The infusion route was kept in the basilic vein with a polyethylene IV catheter of 400 mm in length and 1.8 mm in outside diameter, which was inserted percutaneously and advanced into the right venticle. This catheter was used not only for fluid therapy but also for the sampling of mixed venous blood. Immediately before the start of general anesthesia, expiratory gas, arterial blood and mixed venous blood were collected simultaneously. Arterial blood was sampled by puncturing the femoral artery. Anesthesia was induced by intravenous administration of 3.5 mg/kg of thiarnylal and maintained with nitrous oxide and oxygen. Controlled ventilation was continued mechanically througho u t the operation using muscle relaxant whenever necessary. Additional samplings were done at the time when the patients became conscious but still drowsy immediately after anesthesia and at the subsequent two hours. I n the meantime, the endotracheal tube was left in place. Expiratory oxygen and carbon dioxide concentrations were measured with Sholander's microgas analyzer. Expiratory gas volume was measured with a wet volumeter. PO,, PCO?and pH of arterial and mixed venous blood were measured potentiometically (Radiometer blood gas analyzer BM-3, PHM-72). Oxygen content of blood was measured with Lex 0, Con blood analyzer (Lexington Instrument Corp.). Parameters calculated from the above values and their calculating formula were as follows:
.
V A = V E PEco,/Paco,
Nov.-Dcc. 1917
Pulmonary capillary blood (c') was substituted by fully saturated blood with 100 per cent humidified room air at 37 C.
Results Physiologic parameters measured in this study are summarized in Table I. VE, VA, and Vr tended to increase after transfusion and anesthesia in both the S F group and the D W F group. V A increased from 1.84 I/minute to 3.54 and 3.61 I / minute in the S F group and from 2.09 I/minute to 4.60 and 4.00 I/minute in the DWF group immediately and two hours after anesthesia respectively. An identical change was also observed in V E in the S F group while the relatively less increase was observed in the DWF group. Pao2remained unchanged in the pretransfusion and posttransfusion period in the S F group. Pao8 in the DWF group, however, tended to increase immediately after anesthesia namely, from 68.8 mmHg to 73.0 mmHg, and remained unchanged in the subsequent period. Pacot was 47.5 mmHg in the S F group and 45.4 mmHg in the D W F group before transfusion and anesthesia. Immediately after anesthesia, however, it tended to decrease identically in both groups. Arterial pH in the S F group increased significantly from 7.37 to 7.41 after transfusion. On the other hand, arterial pH in the DWF group remained unchanged at 7.37 to 7.38 throughout the study. These changes in arterial pH in the S F and D W F groups were recognized to be definitely different from each other (0.01 < p < 0.05). F~,,~decreasedfrom 3.12 to 2.62 per cent immediately after anesthesia i n the S F group ( p < 0.01) but not in the D W F group. Although FE,,~ in the S F group increased again to 3.19 per cent two hours after anesthesia, it remained lower than that in the D W F group (0.01 < p < 0.05). Therefore, the difference in Pco2 between arterial blood and expiratory gas (a - E) Pc02 was 2 5 . 2 m m H g a n d 2 1 . O m m H g i n t h e S F a n d DWF groups respectively before transfusion. After transfusion (a - E) Pco2 decreased significantly in the D W F group and minimally in the S F group. These values remained essentially unchanged for the two subsequent hours. Fraction V D / V T which was 0.52 before transfusion in the S F group remained unchanged immediately after transfusion and tended to decrease slightly later. On the other hand, the fraction in the D W F group decreased from 0.47 to 0.33 immediately after transfusion (p < 0.01). Fraction Qs/Qt was 0.31 and 0.30 in the S F and DWF groups respectively before transfusion which was in the higher level than the normal. After transfusion these fractions decreased to 0.25 in the S F
Volume 17 Number6
617
PULMONARY FUNCTION Table 1.
Physiological Parameters in 16 Patients Receiving ACD Whole Blood Through Nylon Mesh Filters (SF) or Dacron Wool Filters (DWF)
Stage
DHa
VE
(l/min)
SF Groupt n=8
1
66.4
f
2 3
67.2 68.5
f
f
1
47.5
2 3
38.5 42.3
1 2 3
DWF Groupt n=8
7.0
68.8
f
9.7
8.4 f 10.0
73.0 73.0
f
11.1 8.8
f
5.0
45.4 f 3.8
f
7.3 5.6
36.7 f 5.1 41.4 f 5.2
7.37 7.41 7.41
f
0.02
f 0.05
7.38 7.37 7.38
f
f 0.05
f f
f
0.03 0.03 0.04
1
12.8
f 2.7
13.6 f 3.5
2 3
13.9 13.9
f f
2.1 2.2
15.8 f 3.0 15.1 f 3.0
2.5
1
10.0
f
2 3
9.6 10.5
f
1 2 3
3.68 7.38 6.80
f
1.5 f 2.4
10.3
* 3.3
l l . 6 * 3.3 11.3* 2.7
f
0.76 3.61 3.85
3.84 =t1.62 6.87 2.45 6.22 f 0.91
f
f
*
1
16.5
1.14
16.3 f 1.06
2 3
17.4 16.9
f
1.11 f 0.85
16.5 f 0.60 16.6 0.44
1
3.1 2
f 0.59
3.32
2 3
2.62 3.19
f
0.63 0.52
3.38 3.63
1 2 3
16.5 28.0 29.2
1 2 3
25.2 19.6 19.3
*
21.0 f 4.5 10.9 2.3 13.7 4.2
1 2 3
160 4 8 230 f 9 4 239 f 107
1 5 7 f 52 2 6 0 f 74 2 3 6 f 32
1 2 3
1.84 f 0.47 3.51 f 1.45 3.61 1.79
2.09 f 1.06 4.60f 1.56 4.00 f 1.04
1 2 3
0.52 0.51 0.45
0.47 f 0.07 0.33 f 0.05 0.36 f 0.09
Cardiac index (1/min/m2)
1 2 3
4.02 4.02 4.28
1.33 1.32
3 . 4 4 f 1.19 4.34 f 2.00 4.33 f 1.43
asmt
1 2 3
0.31 f 0:'14 0.25 f 0.1 7 0.24.t 0.14
0.30 f 0.07 0.15f 0.10 0.24* 0.13
1 2 3
0.32 f 0.07 0.67.t 0.28 0.51 f 0.16
0.41 f 0.10 0.63* 0.17 0.51* 0.13
(a - E) PCOz
(mmHg)
VA
(l/rnin) VD/VT
f
* 9.2
*
18.1 13.3
7.4 4.6 f 4.1
0.1 1 0.08 f 0.07 f f
* 1.03 f f
*
f 0.45 f
0.46
f 0.50
17.Of 11.4 29.4 f 11.4 9.2 26.9
*
* *
Stages: 1 = immediately before the commencement of general anesthesia; 2 = at drowsy state after anesthesia: 3 = at two hours after anesthesia. t mean f standard deviation.
618
TAKAORI ET AL.
group and 0.15 in the DWF group. Particularly the latter decrease was marked and statistically significant ( p < 0.01). Later, however, the fraction remained unchanged in the SF group and tended to increase slightly in the DWF group. The final values were 0.24 in the both groups. (A - a)Po, tended to increase after transfusion in both the SF group and DWF group and then remained unchanged for two hours. On the contrary, VA/Q tended to increase immediately after transfusion and remained in a relatively higher level than that before transfusion in the both groups.
Discussion It has been emphasized that respiratory distress principally characterized by hypoxia follows massive transfusion of stored blood and it may be attributed to diffuse, massive embolism of debris composed of degenerated leukocytes and platelets. Microaggregates 10 to 164 p in size appear in A C D blood and they have been estimated to number to 150 x 10"/ml at the end of preservation of blood for a week. Therefore, fine filters have been developed and they a r e recommended to be used in To evaluate the effects of using fine filters for transfusion, Dawidson et al.' performed exchange transfusion in dogs with heparinized blood stored at 4 C for five days. They observed that Pa,,, tended to decrease slightly in the dogs transfused through a standard filter but not in the dogs transfused through a dacron wool filter. Bischel et ul." reported that Pao9 decreased significantly in patients subjected to hemodialysis by a dialyzer with a standard mesh filter but not with a dacron wool filter. I n the present study, P q , tended to increase in the D W F group and remained unchanged in the SF group after transfusion, although the differences were not significant. However, this does not mean to completely exclude the efficacy of the finer filter. Slightly heavy premedication was done before intubation, and thus their respiration had been depressed moderately. All of ventilatory parameters, such as VE, VA, o r VT, measured in pretransfusion period were at a low level and these tended to return toward normal but re-
TransfuGon No\,.-Drc. 1977
mained low. Reflecting such changes of ventilatory parameters Pa,,? decreased slightly after anesthesia. Such findings will explain the discrepancy of a parallelism between the increase in (A - a)Po, and the increase of Qs/Qt after transfusion. Additional reasons are that arterio-venous oxygen content difference increased due to an increase of Ca,> after transfusion and that patients breathed room air but not pure oxygen during the physiological measurements. Fraction VD/ VT had been elevated before transfusion for the same reason. T h e fraction decreased at the end of anesthesia in the D W F group while it remained unchanged in the SF group at a time when VA, VE, and VT had already increased. Later it tended to decrease slightly but still remained in a higher level than normal o r that in the D W F group. These findings are consistent with an increment of u n per fused-ven ti lated alveoli n a me1y , an occurrence of pulmonary microembolism, in the lungs of the patients to whom stored blood was transfused with a standard filter. DuranceauXshowed that an increase in ventilatory dead space could be utilized as a reliable index of pulmonary microembolism rather than decrease in Pa,,,,. Gray"' classified the progress of pathophysiologic change of respiration caused by embolism into four stages as follows: 1 ) At the first stage immediately after the onset of embolism, alveolar CO, gas content decreases almost to zero in the area where the blood flow has been blocked by embolus. Therefore, the increase in (a - E)Pco, and VD/VT is a primary phenomenon. 2 ) Ventilatory volume decreases due to bronchospasm caused by a reflex from the alveolar CO, concentration lowered'!' o r by serotonin released from aggregated platelets.2" 3) Oxygen saturation of arterial blood will be decreased by opening pulmonary arterio-venous shunt and thus (A - a)Po, increases. 4) Finally, pulmonary arterioles and bronchial arterioles will be connected with shunts vessels and consequently the alveoli whose blood flow has been interrupted will be perfused again.
Volume 17 Nun1 her 6
619
PULMONARY FUNCTION
Therefore, (A - a)Po, remains still in a higher level and (a - E)Pco, will return toward normal. This classification will agree well with pathophysiology of respiration when the second or third branched pulmonary artery will be obstructed by a large thrombus. However, it seems not to agree well with pathophysiology of microembolism of pulmonary arterioles or capillaries, which is seen following massive transfusion of stored blood. Since neither any decrease in Pa,,, any increase in Qs/Qt nor any decrease in V E was found after transfusion in this study, it seemed that occurrence of diffuse microembolism was minimized and ventilatory function of the patients was compensated adequately. Nevertheless concealed decompensation would advance following additional transfusion and respiratory distress would appear gradually in diseased patients. One of the noticeable findings was that pH of arterial blood increased after transfusion in the S F group but not in the DWF group. Dawidson’ and Barrett’ noticed a decrease of pH of blood in the dogs that received exchange blood transfusion through either a standard or polyester mesh filter. However, they found minimized changes in pH of blood in the dogs receiving the exchange blood transfusion with a dacron wool filter. They explained the decrease in pH of blood by the reason that the severe metabolic acidosis would be induced probably due to generalized hypoxia. The increase in pH of arterial blood in the S F group could not be explained as respiratory alkalosis. There was no marked increase in ventilatory volumes and no decrease in Pacovafter transfusion in the S F group. Although serum lactate and other fixed acids have not been measured yet, some of metabolic factors would be expected to affect the changes of pH of blood after transfusion in the SF group. From the above data, it is assumed that the occurrence of concealed pulmonary dysfunction is probably due to diffuse microembolism following transfusion of stored
blood, even in an amount of 1,000 ml. Fortunately no pulmonary distress was noticed in our patients. Nevertheless it may be possible to experience the patient with cardiopulmonary disease who falls into a critical state. Therefore, a fine transfusion filter, such as a dacron wool filter or polyester mesh filter, is desirable for clinical blood transfusion even if transfusion volume does not exceed 1,000 ml. Acknowledgment Transfusion sets with Swank’s filter (dacron wool filter) were supplied kindly from Nikkiso Co. 2-26. Komachi. Hiroshima City, Japan.
References I.
2.
3.
4.
5.
6.
7.
8.
9.
Barrett, J., H. N. Dhurandhar, E. Miller, a n d M . S. Litwin: A comparison in vivo o f dacron wool (Swank) a n d polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion. Ann. Surg. 182:690, 1975. Bennett. S. H.. G. W. Geelhoed. R. K. Aaron, R . T. Solis, a n d R . C. Hoye: Pulmonary injury resulting from perfusion with stored bank blood in the baboon and dog. 1. Surg. Res. 13:295. 1972. Bischel, M. D., F. L. Orrell, B. G. Scoles, J . G. Mohler. a n d B. H . Barbour: Effects o f microemboli blood filtration during hemodialysis. T r a n s . A m . SOC.Artif. Int. O r g a n s 19:492, 1973. Connell. R. S., a n d D. L. Swank: Pulmonary microembolism after blood transfusions-an electron microscopic study. Ann. Surg. 177:40, 1973. Comroe, J. H., Jr., B. Van Lingen, R . C. Stroud. and A. Roncoroni: Reflex a n d direct cardiopulmonary elTects of 5-OH-tryptaminc (serotonin). Their possible role in pulmonary embolism a n d coronary thrombosis. Am. J. Physiol. 173: 379, 1953. Cullen, D. J., a n d L. Ferrarn: Comparative evaluation o f blood filters. Anesthesiology 41:568, 1974. Dawidson, I . , J. A. Barrett. E. Miller, a n d M. S. Litwin: Pulmonary microembolism associated with massive transfusion. Ann. Surg. 18151, 1975. Duranceau, A.. W. C. D e Vries, W. G. Wolfe. and D. C. Sabiston, Jr.: Ventilatory dead space in diagnosis of acute pulmonary embolism. Surg. Forum. 25:229, 1974. Fisher, S. R., A. Duranceau, R. D. Floyd, a n d W. G. Wolfe: Comparative changes in ventila-
TAKAORl ET AL.
10. 11.
12.
13.
14.
15.
16.
17.
tory dead space following micro and massive pulmonary emboli. J. Surg. Res. 20:195, 1976. Gray, F. D.: Pulmonary Embolism. Philadelphia, Lea & Febiger Co., 1966, p. 63. Halmagyi, D. F. J., B. Starzecki, J. McRae, and G . J. Horner: The lung as the main target organ in the acute phase of transfusion reaction in sheep. J. Surg. Res. 3:418, 1963. Jenevein, E. P., and D. L. Weiss: Platelet microemboli associated with massive blood transfusion. Am. J. Pathol. 45:313, 1964. Marshall, B. E., L. R. Soma, J. R. Harp, G. R. Neufeld, H. A. Wurzel, and D. C. Dodd: Pulmonary function after exchange transfusion of stored blood in dogs. Ann. Surg. 179:46. 1974. McNamara, J. J., E. L. Burran, and G . Suehiro: EtTective filtration of banked blood. Surgery 71: 594, 1972. Moseley, R. V.. and D. B. Doty: Death associated with multiple pulmonary emboli soon after battle injury. Ann. Surg. 171:336, 1970. R e d , G . J., A. C. Beall, and S. D. Greenberg: Protection of the pulmonary microvarculature by fine screen blood filtration. Chest 66:4, 1974. Soeter, J. R., G. T. Suehiro, S. Ferrin, P. Nakagawa, and J. McNamara: Comparison of filter-
Transfusion No”.-Dec. 1977
ing efficiency of four new in-line blood transfusion filters. Ann. Surg. 181:114. 1975. 18. Solis, R. T., and M. B. Gibbs: Filtration of the microaggregates in stored blood. Transfusion 12245. 1972. 19. Swank, R. L.: Alteration of blood on storage: Measurement of adhesiveness of “aging” platelets and leukocytes their removal by filtration. N. Engl. J. Med. 265:728, 1961. 20. Swenson, E. W., T. N. Finley, and S. V. Guzman: Unilateral hypoventilation in man during temporary occulusion of one pulmonary artery. J. Clin. Invest. 40:828, 1961.
Masuhiko Takaori, M.D., Professor and Chairman, Department of Anesthesiology, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama, 701, Japan. Nobuyoshi Nakajo, D.D.S.. Assistant Professor, Department of Anesthesiology, Kawasaki Medical School. Takashi Ishii, D.D.S., Research Fellow, Department of Anesthesiology, Kawasaki Medical School:/Present Address-Department of Oral Surgery. University of Osaka, School of Dentistry, 32 Joan-cho, K i t a k u , Osaka City, Japan.
Ventilatory volumes, blood gnses and other aspects of pulmonary function were measured before and after intraoperative transfusion in 16 patients who had undergone operation under general anesthesia. One group consisted o f eight patients transfused w i t h 1275 m l o f stored blood passed through a standard nylon mesh filter (SF group) and the other consisted o f eight patients transfused with stored blood passed through a dacron wool filter (DWF group). Since respiration o f the patients was depressed slightly due to preanesthetic sedation, lowered VE. VT, and el+ vated Paco2,respiratory dead space ratio VD/VT were observed either in the SF or DWF group before anesthesia and transfusion. Even after the recovery o f patients from an~ ~ in ~ the thesia VD/VT remained high and F E decreased SF group. In contrast, VD/VT decreased almost to normal ~ ~ normal ~ in the D W F group. Fraction and F E remained o f physiological shunt Qs/Qt tended to decrease after anesthesia and transfusion either i n the SF or D W F group. The ventilation-perfusion ratio increased relatively more markedly and pHa elevated definitely in the S F group after transfusion. The above data indicate that microembolism occurs after transfusion ofstored blood. even in an amount o f 1.000 ml, with a standard nylon mesh filter and concealed pulmonary dysfunction is observable. Therefore, a fine filter, such as a dacron wool filter or a polyester mesh filter, is r e c o m mended to avoid the pulmonary microembolism and the consequent respiratory distress following the transfusion o f stared blood.
.SWANK indicated that the pulmonary dysfunction following massive blood transfusion could be caused by diffuse pulmonary microembolism.Ig Microemboli were demonstrated microscopically in the lungs of patients who were given large volumes of stored blood.I2 Cornell and Swank.' reported that massive transfusion of stored blood could cause the diffuse microembolism in lungs of dogs experimentally. Reul'" reported that pulmonary arterioles of the lungs in patients who were Received for publication August 23, 1976: accepted November 20, 1976.
transfused with 10 to 63 units of stored blood were filled with fragmented platelets and leukocytes. MoselyI5 reported a patient who died from respiratory insufficiency associated with multiple pulmonary emboli following massive transfusion. Therefore, it has been recommended that a finer mesh filter must be used for prevention of the subsequent respiratory distress. Several experiments have been done to study changes of pulmonary function due to diffuse microembolism in anim a1s."!'. N o study along this line has been done in humans. This study was designed to observe changes of pulmonary function following intraoperative transfusion of stored blood and to evaluate the efficacy of a dacron wool filter for avoiding the respiratory distress after transfusion. Methods
The subjects were 16 patients who had major surgery under general anesthesia and received more than 1,000 mi of blood intrnoperatively. They showed no abnormality in their pulmonary function preoperatively. They were divided at random into two groups. Eight patients received stored ACD blood through standard transfusion sets with nylon mesh filters (SF group). The other eight patients received stored ACD blood through transfusion sets with dacron wool filters (DWF group). The average age of the patients in the SF group was 5 I years and the average age of patients in the DWF group was 44 years. Except for a mastectomy and an amputation of a lower extremity in patients of the SF group all were abdominal operations. Patients of the SF group received from 1,000 to 1,800 m l of blood (average use: 1,275 ml) while the DWF group received from 1,000 to 2,800 ml of blood (average use: 1,375 rnl). All of the patients received 0.5 mg o f atropine
615 Trnnrlurion Nov.-l)ec. 1977
Vulunic 17
Numhcrh
616
Transfusion
TAKORI ET AL
and 15 mg of pentazocine subcutaneously one hour before anesthesia. In addition, 7.5 mg of droperidol and 10 mg of diazepam were given intravenously ten minutes before endotracheal intubation. Topical anesthesia with 2 per cent of lidocaine was done on the oral, pharyngeal, and intratracheal surface and then a cuffed endotracheal tube was intubated. The patient was left to breathe room air spontaneously through a nonrebreathing valve, the expiratory orifice of which was connected to a Douglas bag with a short rubber tube if necessary to collect expiratory gas. The infusion route was kept in the basilic vein with a polyethylene IV catheter of 400 mm in length and 1.8 mm in outside diameter, which was inserted percutaneously and advanced into the right venticle. This catheter was used not only for fluid therapy but also for the sampling of mixed venous blood. Immediately before the start of general anesthesia, expiratory gas, arterial blood and mixed venous blood were collected simultaneously. Arterial blood was sampled by puncturing the femoral artery. Anesthesia was induced by intravenous administration of 3.5 mg/kg of thiarnylal and maintained with nitrous oxide and oxygen. Controlled ventilation was continued mechanically througho u t the operation using muscle relaxant whenever necessary. Additional samplings were done at the time when the patients became conscious but still drowsy immediately after anesthesia and at the subsequent two hours. I n the meantime, the endotracheal tube was left in place. Expiratory oxygen and carbon dioxide concentrations were measured with Sholander's microgas analyzer. Expiratory gas volume was measured with a wet volumeter. PO,, PCO?and pH of arterial and mixed venous blood were measured potentiometically (Radiometer blood gas analyzer BM-3, PHM-72). Oxygen content of blood was measured with Lex 0, Con blood analyzer (Lexington Instrument Corp.). Parameters calculated from the above values and their calculating formula were as follows:
.
V A = V E PEco,/Paco,
Nov.-Dcc. 1917
Pulmonary capillary blood (c') was substituted by fully saturated blood with 100 per cent humidified room air at 37 C.
Results Physiologic parameters measured in this study are summarized in Table I. VE, VA, and Vr tended to increase after transfusion and anesthesia in both the S F group and the D W F group. V A increased from 1.84 I/minute to 3.54 and 3.61 I / minute in the S F group and from 2.09 I/minute to 4.60 and 4.00 I/minute in the DWF group immediately and two hours after anesthesia respectively. An identical change was also observed in V E in the S F group while the relatively less increase was observed in the DWF group. Pao2remained unchanged in the pretransfusion and posttransfusion period in the S F group. Pao8 in the DWF group, however, tended to increase immediately after anesthesia namely, from 68.8 mmHg to 73.0 mmHg, and remained unchanged in the subsequent period. Pacot was 47.5 mmHg in the S F group and 45.4 mmHg in the D W F group before transfusion and anesthesia. Immediately after anesthesia, however, it tended to decrease identically in both groups. Arterial pH in the S F group increased significantly from 7.37 to 7.41 after transfusion. On the other hand, arterial pH in the DWF group remained unchanged at 7.37 to 7.38 throughout the study. These changes in arterial pH in the S F and D W F groups were recognized to be definitely different from each other (0.01 < p < 0.05). F~,,~decreasedfrom 3.12 to 2.62 per cent immediately after anesthesia i n the S F group ( p < 0.01) but not in the D W F group. Although FE,,~ in the S F group increased again to 3.19 per cent two hours after anesthesia, it remained lower than that in the D W F group (0.01 < p < 0.05). Therefore, the difference in Pco2 between arterial blood and expiratory gas (a - E) Pc02 was 2 5 . 2 m m H g a n d 2 1 . O m m H g i n t h e S F a n d DWF groups respectively before transfusion. After transfusion (a - E) Pco2 decreased significantly in the D W F group and minimally in the S F group. These values remained essentially unchanged for the two subsequent hours. Fraction V D / V T which was 0.52 before transfusion in the S F group remained unchanged immediately after transfusion and tended to decrease slightly later. On the other hand, the fraction in the D W F group decreased from 0.47 to 0.33 immediately after transfusion (p < 0.01). Fraction Qs/Qt was 0.31 and 0.30 in the S F and DWF groups respectively before transfusion which was in the higher level than the normal. After transfusion these fractions decreased to 0.25 in the S F
Volume 17 Number6
617
PULMONARY FUNCTION Table 1.
Physiological Parameters in 16 Patients Receiving ACD Whole Blood Through Nylon Mesh Filters (SF) or Dacron Wool Filters (DWF)
Stage
DHa
VE
(l/min)
SF Groupt n=8
1
66.4
f
2 3
67.2 68.5
f
f
1
47.5
2 3
38.5 42.3
1 2 3
DWF Groupt n=8
7.0
68.8
f
9.7
8.4 f 10.0
73.0 73.0
f
11.1 8.8
f
5.0
45.4 f 3.8
f
7.3 5.6
36.7 f 5.1 41.4 f 5.2
7.37 7.41 7.41
f
0.02
f 0.05
7.38 7.37 7.38
f
f 0.05
f f
f
0.03 0.03 0.04
1
12.8
f 2.7
13.6 f 3.5
2 3
13.9 13.9
f f
2.1 2.2
15.8 f 3.0 15.1 f 3.0
2.5
1
10.0
f
2 3
9.6 10.5
f
1 2 3
3.68 7.38 6.80
f
1.5 f 2.4
10.3
* 3.3
l l . 6 * 3.3 11.3* 2.7
f
0.76 3.61 3.85
3.84 =t1.62 6.87 2.45 6.22 f 0.91
f
f
*
1
16.5
1.14
16.3 f 1.06
2 3
17.4 16.9
f
1.11 f 0.85
16.5 f 0.60 16.6 0.44
1
3.1 2
f 0.59
3.32
2 3
2.62 3.19
f
0.63 0.52
3.38 3.63
1 2 3
16.5 28.0 29.2
1 2 3
25.2 19.6 19.3
*
21.0 f 4.5 10.9 2.3 13.7 4.2
1 2 3
160 4 8 230 f 9 4 239 f 107
1 5 7 f 52 2 6 0 f 74 2 3 6 f 32
1 2 3
1.84 f 0.47 3.51 f 1.45 3.61 1.79
2.09 f 1.06 4.60f 1.56 4.00 f 1.04
1 2 3
0.52 0.51 0.45
0.47 f 0.07 0.33 f 0.05 0.36 f 0.09
Cardiac index (1/min/m2)
1 2 3
4.02 4.02 4.28
1.33 1.32
3 . 4 4 f 1.19 4.34 f 2.00 4.33 f 1.43
asmt
1 2 3
0.31 f 0:'14 0.25 f 0.1 7 0.24.t 0.14
0.30 f 0.07 0.15f 0.10 0.24* 0.13
1 2 3
0.32 f 0.07 0.67.t 0.28 0.51 f 0.16
0.41 f 0.10 0.63* 0.17 0.51* 0.13
(a - E) PCOz
(mmHg)
VA
(l/rnin) VD/VT
f
* 9.2
*
18.1 13.3
7.4 4.6 f 4.1
0.1 1 0.08 f 0.07 f f
* 1.03 f f
*
f 0.45 f
0.46
f 0.50
17.Of 11.4 29.4 f 11.4 9.2 26.9
*
* *
Stages: 1 = immediately before the commencement of general anesthesia; 2 = at drowsy state after anesthesia: 3 = at two hours after anesthesia. t mean f standard deviation.
618
TAKAORI ET AL.
group and 0.15 in the DWF group. Particularly the latter decrease was marked and statistically significant ( p < 0.01). Later, however, the fraction remained unchanged in the SF group and tended to increase slightly in the DWF group. The final values were 0.24 in the both groups. (A - a)Po, tended to increase after transfusion in both the SF group and DWF group and then remained unchanged for two hours. On the contrary, VA/Q tended to increase immediately after transfusion and remained in a relatively higher level than that before transfusion in the both groups.
Discussion It has been emphasized that respiratory distress principally characterized by hypoxia follows massive transfusion of stored blood and it may be attributed to diffuse, massive embolism of debris composed of degenerated leukocytes and platelets. Microaggregates 10 to 164 p in size appear in A C D blood and they have been estimated to number to 150 x 10"/ml at the end of preservation of blood for a week. Therefore, fine filters have been developed and they a r e recommended to be used in To evaluate the effects of using fine filters for transfusion, Dawidson et al.' performed exchange transfusion in dogs with heparinized blood stored at 4 C for five days. They observed that Pa,,, tended to decrease slightly in the dogs transfused through a standard filter but not in the dogs transfused through a dacron wool filter. Bischel et ul." reported that Pao9 decreased significantly in patients subjected to hemodialysis by a dialyzer with a standard mesh filter but not with a dacron wool filter. I n the present study, P q , tended to increase in the D W F group and remained unchanged in the SF group after transfusion, although the differences were not significant. However, this does not mean to completely exclude the efficacy of the finer filter. Slightly heavy premedication was done before intubation, and thus their respiration had been depressed moderately. All of ventilatory parameters, such as VE, VA, o r VT, measured in pretransfusion period were at a low level and these tended to return toward normal but re-
TransfuGon No\,.-Drc. 1977
mained low. Reflecting such changes of ventilatory parameters Pa,,? decreased slightly after anesthesia. Such findings will explain the discrepancy of a parallelism between the increase in (A - a)Po, and the increase of Qs/Qt after transfusion. Additional reasons are that arterio-venous oxygen content difference increased due to an increase of Ca,> after transfusion and that patients breathed room air but not pure oxygen during the physiological measurements. Fraction VD/ VT had been elevated before transfusion for the same reason. T h e fraction decreased at the end of anesthesia in the D W F group while it remained unchanged in the SF group at a time when VA, VE, and VT had already increased. Later it tended to decrease slightly but still remained in a higher level than normal o r that in the D W F group. These findings are consistent with an increment of u n per fused-ven ti lated alveoli n a me1y , an occurrence of pulmonary microembolism, in the lungs of the patients to whom stored blood was transfused with a standard filter. DuranceauXshowed that an increase in ventilatory dead space could be utilized as a reliable index of pulmonary microembolism rather than decrease in Pa,,,,. Gray"' classified the progress of pathophysiologic change of respiration caused by embolism into four stages as follows: 1 ) At the first stage immediately after the onset of embolism, alveolar CO, gas content decreases almost to zero in the area where the blood flow has been blocked by embolus. Therefore, the increase in (a - E)Pco, and VD/VT is a primary phenomenon. 2 ) Ventilatory volume decreases due to bronchospasm caused by a reflex from the alveolar CO, concentration lowered'!' o r by serotonin released from aggregated platelets.2" 3) Oxygen saturation of arterial blood will be decreased by opening pulmonary arterio-venous shunt and thus (A - a)Po, increases. 4) Finally, pulmonary arterioles and bronchial arterioles will be connected with shunts vessels and consequently the alveoli whose blood flow has been interrupted will be perfused again.
Volume 17 Nun1 her 6
619
PULMONARY FUNCTION
Therefore, (A - a)Po, remains still in a higher level and (a - E)Pco, will return toward normal. This classification will agree well with pathophysiology of respiration when the second or third branched pulmonary artery will be obstructed by a large thrombus. However, it seems not to agree well with pathophysiology of microembolism of pulmonary arterioles or capillaries, which is seen following massive transfusion of stored blood. Since neither any decrease in Pa,,, any increase in Qs/Qt nor any decrease in V E was found after transfusion in this study, it seemed that occurrence of diffuse microembolism was minimized and ventilatory function of the patients was compensated adequately. Nevertheless concealed decompensation would advance following additional transfusion and respiratory distress would appear gradually in diseased patients. One of the noticeable findings was that pH of arterial blood increased after transfusion in the S F group but not in the DWF group. Dawidson’ and Barrett’ noticed a decrease of pH of blood in the dogs that received exchange blood transfusion through either a standard or polyester mesh filter. However, they found minimized changes in pH of blood in the dogs receiving the exchange blood transfusion with a dacron wool filter. They explained the decrease in pH of blood by the reason that the severe metabolic acidosis would be induced probably due to generalized hypoxia. The increase in pH of arterial blood in the S F group could not be explained as respiratory alkalosis. There was no marked increase in ventilatory volumes and no decrease in Pacovafter transfusion in the S F group. Although serum lactate and other fixed acids have not been measured yet, some of metabolic factors would be expected to affect the changes of pH of blood after transfusion in the SF group. From the above data, it is assumed that the occurrence of concealed pulmonary dysfunction is probably due to diffuse microembolism following transfusion of stored
blood, even in an amount of 1,000 ml. Fortunately no pulmonary distress was noticed in our patients. Nevertheless it may be possible to experience the patient with cardiopulmonary disease who falls into a critical state. Therefore, a fine transfusion filter, such as a dacron wool filter or polyester mesh filter, is desirable for clinical blood transfusion even if transfusion volume does not exceed 1,000 ml. Acknowledgment Transfusion sets with Swank’s filter (dacron wool filter) were supplied kindly from Nikkiso Co. 2-26. Komachi. Hiroshima City, Japan.
References I.
2.
3.
4.
5.
6.
7.
8.
9.
Barrett, J., H. N. Dhurandhar, E. Miller, a n d M . S. Litwin: A comparison in vivo o f dacron wool (Swank) a n d polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion. Ann. Surg. 182:690, 1975. Bennett. S. H.. G. W. Geelhoed. R. K. Aaron, R . T. Solis, a n d R . C. Hoye: Pulmonary injury resulting from perfusion with stored bank blood in the baboon and dog. 1. Surg. Res. 13:295. 1972. Bischel, M. D., F. L. Orrell, B. G. Scoles, J . G. Mohler. a n d B. H . Barbour: Effects o f microemboli blood filtration during hemodialysis. T r a n s . A m . SOC.Artif. Int. O r g a n s 19:492, 1973. Connell. R. S., a n d D. L. Swank: Pulmonary microembolism after blood transfusions-an electron microscopic study. Ann. Surg. 177:40, 1973. Comroe, J. H., Jr., B. Van Lingen, R . C. Stroud. and A. Roncoroni: Reflex a n d direct cardiopulmonary elTects of 5-OH-tryptaminc (serotonin). Their possible role in pulmonary embolism a n d coronary thrombosis. Am. J. Physiol. 173: 379, 1953. Cullen, D. J., a n d L. Ferrarn: Comparative evaluation o f blood filters. Anesthesiology 41:568, 1974. Dawidson, I . , J. A. Barrett. E. Miller, a n d M. S. Litwin: Pulmonary microembolism associated with massive transfusion. Ann. Surg. 18151, 1975. Duranceau, A.. W. C. D e Vries, W. G. Wolfe. and D. C. Sabiston, Jr.: Ventilatory dead space in diagnosis of acute pulmonary embolism. Surg. Forum. 25:229, 1974. Fisher, S. R., A. Duranceau, R. D. Floyd, a n d W. G. Wolfe: Comparative changes in ventila-
TAKAORl ET AL.
10. 11.
12.
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14.
15.
16.
17.
tory dead space following micro and massive pulmonary emboli. J. Surg. Res. 20:195, 1976. Gray, F. D.: Pulmonary Embolism. Philadelphia, Lea & Febiger Co., 1966, p. 63. Halmagyi, D. F. J., B. Starzecki, J. McRae, and G . J. Horner: The lung as the main target organ in the acute phase of transfusion reaction in sheep. J. Surg. Res. 3:418, 1963. Jenevein, E. P., and D. L. Weiss: Platelet microemboli associated with massive blood transfusion. Am. J. Pathol. 45:313, 1964. Marshall, B. E., L. R. Soma, J. R. Harp, G. R. Neufeld, H. A. Wurzel, and D. C. Dodd: Pulmonary function after exchange transfusion of stored blood in dogs. Ann. Surg. 179:46. 1974. McNamara, J. J., E. L. Burran, and G . Suehiro: EtTective filtration of banked blood. Surgery 71: 594, 1972. Moseley, R. V.. and D. B. Doty: Death associated with multiple pulmonary emboli soon after battle injury. Ann. Surg. 171:336, 1970. R e d , G . J., A. C. Beall, and S. D. Greenberg: Protection of the pulmonary microvarculature by fine screen blood filtration. Chest 66:4, 1974. Soeter, J. R., G. T. Suehiro, S. Ferrin, P. Nakagawa, and J. McNamara: Comparison of filter-
Transfusion No”.-Dec. 1977
ing efficiency of four new in-line blood transfusion filters. Ann. Surg. 181:114. 1975. 18. Solis, R. T., and M. B. Gibbs: Filtration of the microaggregates in stored blood. Transfusion 12245. 1972. 19. Swank, R. L.: Alteration of blood on storage: Measurement of adhesiveness of “aging” platelets and leukocytes their removal by filtration. N. Engl. J. Med. 265:728, 1961. 20. Swenson, E. W., T. N. Finley, and S. V. Guzman: Unilateral hypoventilation in man during temporary occulusion of one pulmonary artery. J. Clin. Invest. 40:828, 1961.
Masuhiko Takaori, M.D., Professor and Chairman, Department of Anesthesiology, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama, 701, Japan. Nobuyoshi Nakajo, D.D.S.. Assistant Professor, Department of Anesthesiology, Kawasaki Medical School. Takashi Ishii, D.D.S., Research Fellow, Department of Anesthesiology, Kawasaki Medical School:/Present Address-Department of Oral Surgery. University of Osaka, School of Dentistry, 32 Joan-cho, K i t a k u , Osaka City, Japan.
