An in Vivo Evaluation of Microaggregate Blood Filtration During Total Hip Replacement EDWARD L. SNYDER, M.D.,* PATRICIA S. UNDERWOOD, M.D.,t MORTON SPIVACK, M.D.,* LAWRENCE DEANGELIS, M.D.,t EDWARD T. HABERMANN, M.D.4 In order to evaluate the effect of microaggregate blood filtration on pulmonary status, hemostatic status, and incidence of infection, a prospective study was performed on patients undergoing elective total hip replacement for osteoarthritis. Forty patients were randomized to either a 260 micron standard filter group or a 20 micron microaggregate filter group. Patients were monitored pre- and postoperatively for changes in arterial blood gases and in vitro test of hemostasis. Postoperative measurements were also made of the total volume of blood collected from the operative wound drain and of the number of infections incurred by patients in the two filter groups. Average transfusion was 4.0 units for the standard filter group and 4.6 units for the microaggregate filter group. Results showed that postoperatively, either immediately or after 48 hours, there were no statistically significant differences (p > 0.05) between either filter group for any of the tests of pulmonary or hemostatic function evaluated. For infection no trends were found to suggest that microaggregate filters conveyed any protective effect. These data suggest that routine microaggregate blood filtration of up to 5 units of blood is not required.
D ATA FROM MILITARY6 and civilian9 1" trauma studies suggest that when transfused in large quantities, microaggregates play a role in the development of the adult respiratory distress syndrome. Furthermore, Solis and Gibbs12 have postulated that infusion of microaggregates might produce a blockade of the reticuloendothelial system and thus contribute to the bleeding and infection seen after massive blood transfusion. Few studies have evaluated these parameters in patients receiving low volume elective transfusions. To assess the in vivo effect of microaggregate blood
*Department of Internal
Medicine. t Department of Anesthesiology. t Department of Orthopaedics. Presented in part at the Annual Meeting of the American Association of Blood Banks, November 4-9, 1978, New Orleans,
Louisiana. Supported in part by National Research Service Award 5 T32 HL07080 USPHS, (Dr. Snyder) and a grant from Bentley Laboratories, Inc. Reprint requests: Edward L. Snyder. M.D., Yale-New Haven Hospital, 789 Howard Avenue, New Haven, Connecticut 06504.
From the Departments of Internal Medicine, Anesthesiology, and Orthopaedics, Montefiore Hospital and Medical Center, Bronx, New York
filtration (MABF) on pulmonary function, hemostatic function, and incidence of infection, we designed a prospective randomized study on patients undergoing elective total hip replacement.
Materials and Methods Patient Selection Criteria From June 1977 through July 1978, using a table of random numbers, 40 patients undergoing elective total hip replacement for primary or secondary osteoarthritis were assigned to one of two filter groups (Table 1). Patients paired with an even number (SF group; n = 20) received all blood transfusions through a large pore 260,u standard filter (Saftifilter 834-30, Cutter Laboratories, Berkeley, CA). The other patients, matched with an odd number, (MF group; n = 20) received blood infused through a 20,u microaggregate blood filter (PFF-100, Bentley Laboratories, Irvine, CA). To maintain uniformity between the two patient groups the following criteria were imposed: 1) Age: All patients were over 40 years of age. 2) Surgical history: All patients were scheduled for elective total hip replacement for either primary degenerative osteoarthritis or osteoarthritis secondary to previous hip surgery or trauma. 3) Medical history: Patients were free of clinically detectable renal, cardiovascular, pulmonary, hematologic, or systemic disease. Patients were excluded from the protocol if any of the following abnormalities were present: Renal: History of acute or chronic renal disease, serum creatinine over 1.3 mg/dl. Cardiovascular: History of right or left sided congestive heart failure, angina pectoris, recent cere-
0003-4932/79/0700/0075 $00.75 C) J. B. Lippincott Company
75
Ann. Surg.
SNYDER AND OTHERS
76 TABLE 1. Clinical Material
Patients Mean age (range) Sex (M/F) Mean transfusion (range)
MF-20,u Filter
SF-260,u Filter
20 69 (40-86) 3/17 4.6 (2-9)
20 63 (40-81) 3/17 4.0 (2-7)
brovascular accident, clinical evidence of extensive peripheral vascular disease, EKG evidence of myocardial ischemia or acute cardiac arrhythmia, radiographic evidence of cardiomegaly, systolic hypertension over 180 mmHg and diastolic hypertension over 106 mmHg. Pulmonary: History of obstructive or restrictive lung disease, chronic bronchitis, use of over one pack of cigarettes per day, abnormal chest radiograph, arterial blood gas on room air (FiO2-.21) showing a Paco2 over 42 mmHg and a Pao2 less than 70 mmHg. Hematologic: History of chronic bleeding diathesis, abnormal preoperative platelet count or prothrombin time. Systemic: Presence of any systemic illness i.e., sickle cell anemia, rheumatoid arthritis, or carcinoma.
Parameters Studied
Evaluation of MABF in these surgical patients included: 1) Hematologic (preoperative and two hours postoperative): hematocrit, hemoglobin, white blood count, plasma hemoglobin. 2) Clinical chemistry (preoperative and two hours postoperative): serum sodium, potassium, albumin, globulin. 3) Hemostasis (preoperative and two hours postoperative): platelet count, prothrombin time; volume of blood collected from the postoperative wound drain (1-72 hours postoperatively). 4) Pulmonary (preoperative, intraoperative, two hours
Protocol
Informed consent was obtained from all patients in the study in accordance with the recommendations and approval of the Human Subjects Committee of Montefiore Hospital and Medical Center. Baseline preoperative clinical laboratory studies were drawn prior to surgery (Table 2). Preoperative arterial blood gases (PREOP) were obtained immediately prior to intubation while the patient was awake and breathing room air (FiO2-.21). After induction and maintenance of anesthesia using a neurolept technique the patient was placed on a respirator with FiO2 of .33. Thirty minutes after intubation, during the initial surgical skin incision, a blood gas (SI) was obtained through an indwelling radial artery catheter previously inserted for routine intraoperative patient monitoring. Additional blood gases were subsequently obtained after each unit of blood and 15 minutes after each of the two parts of the Charnley hip prosthesis were cemented into place using methylmethacrylate bone cement (MMA- 1, MMA-2). During surgery, if the FiO2 was altered for any reason, it was reset to .33 for 20 minutes prior = 20)
± SEM
Preoperative*
Hematocrit (%) Hemoglobin (g/dl) W.B.C. (x1011/) Platelets (x109/l) Plasma hemoglobin (mg/dl) Sodium (mEq/l) Potassium (mEq/l) Albumin (g/dl) Globulin (g/dl) Prothrombin time (sec)t *
P > O.OS (N.S-)-
20,u-MF 38.5 13.0 7.3 208.5 4.5 141 4.3 4.3 3.0
+ ± ± ± ± ± ± 10
0.9 0.4 0.5 12.4 0.5 0.6 0.1 0.1 0.1
July 1979
postoperative, 48 hours postoperative): arterial pH, Po2, Pco2. 5) Infection: postoperatively until discharge patients were monitored for development of infection using the following criteria: a) Urinary tract infection: Pyuria on urinanalysis with clean catch urine samples sent for culture reported as having over 100,000 bacterial colonies for females, or over 10,000 colonies for males. b) Septicemia: Positive blood cultures. c) Operative wound infection: clinical signs of infection and/or inflammation with positive bacterial cultures. d) Pulmonary infection: clinical and/or radiographic evidence of consolidation or infiltration with positive sputum gram stain or culture.
TABLE 2. Clinical Laboratory Tests (n
Parameter
*
2H Postoperative*
20,-MF
260,u-SF 37.8 12.8 7.7 228.6 5.0 141 4.2 4.1 3.2
± ± ± ± ± ± ±
33.5 11.4 12.2 148.3 6.7 136 3.7 3.5 2.0
1.3 0.4 0.6 14.8 0.7 0.8 0.1 0.1 0.1
11
10
t Normal control
± ± ± ± ± ± ±
=
10 seconds.
1.0 0.4 1.1 13.6 0.7 1.1 0.1 0.1 0.1
2604-SF 35.6 12.0 15.9 163.6 6.4 136 3.7 3.5 2.3
± ± ± ± ± ± ± ± ±
11
1.1 0.4 1.6 18.7 0.7 0.9 0.1 0.1 0.1
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MICROAGGREGATE BLOOD FILTRATION
I
77
TABLE 3. Preoperative and Postoperative Blood Gas Results (FiO2-.21)
MF-20i. (n = 20)
SF-260,a Filter*
(n = 20) 2H-Post
Preop 7.41 + .01 36.5 + 1.2 80.4 + 2.5 *
Filter* + S.E.M.
7.39 37.5 71.1
--
+ +
(n = 13) 48H-Post
.01 0.9 3.0
7.45 32.3 73.5
+ + +
(n = 20)
Preop
.01 0.8 3.2
pHa
7.40 + .01 38.5 -+- 0.8 80.2 + 2.3
Paco2 Pao2
+
S.E.M.
(n = 20) 2H-Post 7.36 40.2 71.5
+ -++
.01 1.0 2.0
(n = 14) 48H-Post 7.44 33.6 75.0
+ + +
.01 0.9 2.4
p > 0.05 (N.S.)
to resampling. A final intraoperative blood gas (SC) obtained at the time of skin closure (FiO2-.33)
was
following completion of the procedure. Two hours postoperatively, the various blood tests listed in Table 2, and another blood gas (2H-POST) were obtained (FiO2-.21). For most patients a blood gas was also obtained 48 hours postoperatively (48H-POST) via a single radial artery puncture with the patient breathing room air (FiO2-.21). All blood drainage collected via a Hemovac wound drain (Snyder Manufacturing Company, New Philadelphia, Ohio) was measured. The drain was routinely left indwelling up to 72 hours. As part of routine care all patients received aminoglycoside antibiotics intraoperatively and for 24-48 hours postoperatively. All patients received intensive postoperative pulmonary toilette, and were encouraged to begin early ambulation. Urine cultures were collected from all patients who developed a fever during the first two postoperative days. Subsequent cultures were obtained if the patient again became febrile, or developed clinical symptoms of urinary tract infection. Blood cultures were drawn on patients with either a high postoperative fever or with a new or persisting fever lasting over 24-48 hours. Cultures of the operative wound were taken from patients with clinical signs of infection such as delayed wound closure associated with erythema and serous drainage. Pulmonary status was clinically monitored each day. Chest radiographs and sputum cultures were obtained from patients with postoperative fever and cough in whom a pneumonic process was suspected. This type of evaluation was initiated whenever a clinical diagnosis
of pneumonia was considered in a patient, regardless of the amount of time that had elapsed since the day of surgery. All transfused bloods were at least 12 days old. Collected data was analyzed using a parametric twotailed Student's t-test for independent sets, and a nonparametric two-tailed Wilcoxson rank-sum test. The level of statistical significance used was p < 0.05. Results Evaluation of the clinical material is shown in Table 1. The comparison of clinical laboratory tests was made preoperatively to document additional similarity between the two filter groups, and postoperatively to exclude any harmful effects from the microaggregate filtration of blood in the amounts used in the study (Table 2). As seen there were no statistically significant differences between the two groups of surgical patients. Similarity in the preoperative and postoperative plasma hemoglobins for the two groups excluded clinically significant MABF-induced hemolysis. Arterial blood gas results (Table 3) showed that on room air (FiO2-.21) preoperatively and 2 hours postoperatively there were no differences (p > 0.05) between the two groups for either arterial pH, Pco2 or Po2. Blood gases sampled 48 hours postoperatively also failed to show any variation between the two sample populations. Similarly, arterial blood gases taken intraoperatively (Table 4) with patients intubated (FiO2-.33) showed no difference between samples taken at the start of surgery (SI) and those obtained at the end of the operation during skin closure (SC) after all blood transfusions had been given. Blood gases
TABLE 4. Intraoperative Blood Gas Results (FiO2-.33)
MF-20,u Filter (n
=
20)*
+
SF-260,u. Filter (n = 20)*
S.E.M.
SI
MMA-1
MMA-2
SC
7.43 + .01 33.7 ± 1.2 115.7 ± 4.2
7.41 + .01 33.8 ± 1.3 115.7 + 5.6
7.41 + .01 34.9 ± 1.2 108 ± 6.0
7.41 + .01 35.1 ± 1.2 114.6 ± 6.2
*
p > 0.05 (N.S.).
pHa
PacO2 Pao2
+
S.E.M.
SI
MMA-1
MMA-2
SC
7.41 + .01 35.9 ± 0.9 121.3 ± 6.0
7.41 ± .01 33.7 ± 1.2 112.6 ± 5.5
7.41 ± .01 34.5 ± 1.3 112.2 ± 6.2
7.40 ± .01 35.3 ± 1.2 119.1 ± 6.7
Ann.
SNYDER AND OTHERS
78 TABLE 5. Postoperative Bleeding
MF-20,u Filter* (n =20) 644
54 ml
SF-260,u Filter* (n 621
20) 69 ml
* (p > 0.05) (N.S.).
obtained five minutes after the hip prothesis was cemented into place (MMA- 1, MMA-2) were unchanged from the values obtained during skin incision (SI). The volume of fluid intake and output was monitored for 48 hours postoperatively and showed no statistically significant differences (p > 0.05) between the two groups. None of the patients in either filter group developed clinical signs of respiratory distress postoperatively. Patient tendency to hemorrhage (Table 5) evaluated by measurement of the total drainage from the operative wound site during the 72 hours that the wound drain remained indwelling, showed that the total volumes collected from both filter groups were comparable. Routine evaluation of all patients in both filter groups revealed no evidence of preoperative infection. All patients entered into the study were afebrile, had chest radiographs which were negative for acute infiltration, urinanalyses which were negative for active urinary tract infection, and white blood counts which were within the normal limits for the laboratory. Postoperatively all patients became febrile but defervesced within 72 hours unless a bacterial infection was found (Table 6). These transient febrile episodes were attributed to an inflammatory response to surgery. Postoperative urine cultures were obtained from all 40 patients in both groups during the first 24-48 hours and subsequently as described in the protocol. At the end of the study only six infections had been documented in the 20, filter group and four infections verified in the 260, filter group. Exclusion of those patients who had indwelling bladder catheters reduced the incidence of urinary tract infection to only two patients in each filter group. No patient developed a bacteriologically proven deep wound infection during the course of the study, and in only one patient was the diagnosis considered. Although a superficial wound infection was suspected in 11 of the 40 study patients, only seven of the 11 patients evaluated had positive bacterial cultures. Staphylococcus epidermidis was the predominant organism cultured from the skin of three patients in the MF group and three of four patients in the SF group (Table 6). Blood cultures were obtained from 35% of the patients in the 20,u MF group and 3 0% of the patients in the 260, SF group. All of the cultures were sterile.
Surg. July 1979 *
Postoperatively none of the patients in either group developed respiratory distress. During the course of the study chest radiographs were ordered for seven patients in the microaggregate filter group and six patients in the standard filter group. Although atelectasis was reported on several of the postoperative films, none of the radiographs disclosed any evidence of acute infiltration or consolidation. Sputum cultures on the patients studied were reported as "'normal flora." Discussion For the parameters investigated in our study no evidence was found that any benefit accrued to patients who received microaggregate filtered blood in the amounts used. We evaluated two sets of blood gas determinations, one set pre- and postoperatively while the patients were spontaneously breathing room air (FiO2-.21), and the second set intraoperatively during anesthesia (FiO2-.33). This provided a method of double checking the results since blood gases collected during spontaneous respiration could have been influenced by hypoventilation either from preoperative sedation or from postoperative incisional pain. No discrepancies between the two sets of data were found. No reduction in postoperative hemorrhage was found in those patients receiving microaggregate filtered blood. For infections the numbers were too small to permit statistically significant conclusions.8 Rather we were interested in trends which might imply a protective effect attributable to use of microaggregate filters. No such trends were seen. Although a blockade of the reticuloendothelial system may be involved in the increased bleeding and infection reported after massive transfusions, we could not document that either of these clinical findings occurred after the transfusion of up to five units of blood in our patients. TABLE 6. Postoperative Infection
MF-20,u Filter (n = 20)
Parameter Fever (+ 38°) Septicemia (blood cultures) Deep wound infection Superficial wound infection Pneumonia Urinary tract infection total without catheter
SF-260,u Filter (n = 20)
Patients Evaluated
Patients Positive
Patients Evaluated
20
20
20
20
7
0
6
0
1
0
0
0
5 7
3* 0
6 6
4** 0
20 7
6 2t
20 8
Patients Positive
4
2t
*Staphylococcus epidermidis -3. **Staphylococcus epidermidis -3; Proteus sp. -1. tProteus sp. -2. tPseudomonas aeruginosa -2.
Vol. 190 * No. I
MICROAGGREGATE BLOOD FILTRATION
The number of microaggregates infused with four-five units of blood (3-3.5 x 108) may have been insufficient to affect the reticuloendothelial system.11 Alternatively, additional factors not detectable in our patients such as sustained hypotension, disseminated intravascular coagulation or hypovolemic shock may be playing a major causative role in the development of the bleeding and infection seen in massively transfused trauma patients. Our study documented a lack of changes in arterial blood gases in the SF group up to 48 hours posttransfusion by which time significant changes in pulmonary gas exchange should have become detectable. Sensitive tests of pulmonary function have been able to detect some alterations in gas exchange after low volume transfusions, however, these changes have not been found consistently. For patients transfused with less than 3000 ml of blood, Takaori et al.13 reported some adverse changes in pulmonary dead space (VD/ VT) but no alterations in pulmonary shunting (Qs/Qt). Barrett et al.1 found abnormalities in Qs/Qt in patients receiving several units of blood through a standard 170,t filter, but none in patients receiving microaggregate filtered blood. Virgilio et al.14 however, reported finding no alterations in pulmonary function tests for 20 patients receiving an average of six-seven units of blood through a 170,u filter. None of the patients described in these three studies developed any clinical signs of respiratory distress. The relationship between transfusion and subsequent hypoxemia was recently examined in a retrospective analysis of Vietnam combat casualties. Collins' group4 concluded that differences in Pao2 noted in soldiers studied were more likely related to the type and the magnitude of injury sustained than the amount of blood
transfused. Of the over 6 million units of blood estimated to be transfused yearly in the United States,7 the majority of patients receive less than four units. Since patients receiving low volume transfusions through standard pore filters are clinically asymptomatic with no evidence of hypoxemia, there seems to be little scientific justification for the proposal made by some authors5 13 that MABF should be used routinely regardless of the volume of blood infused. Even the data reported by Reul9'10 showing a need for MABF in massively transfused patients has been questioned, due to differences between the two groups of patients compared.2'3 Economic factors also enter into the decision to use MABF for all transfusions. At present, a MABF-administration set costs several dollars more than a standard blood administration set.
79
It is possible that while the healthy lung can compensate for microaggregate emboli, a diseased lung cannot. Controlled studies evaluating the effect of low volume transfusions in patients with compromised pulmonary function are lacking; routine use of MABF in such patients may be of value. Based on our study of arterial blood gases, bleeding tendency, and infection rate, we conclude that routine microaggregate blood filtration of up to five units of blood is not required.
Acknowledgments The authors wish to thank Mrs. R. Condon for excellent secretarial assistance.
References 1. Barrett, J., Tahir, A. H. and Litwin, M. S.: Increased Pulmonary Arteriovenous Shunting in Humans Following Blood Transfusion. Arch. Surg., 113:947, 1978. 2. Bredenberg, C. E.: Does a Relationship exist between Massive Blood Transfusions and the Adult Respiratory Distress Syndrome? Vox Sang., 32:311, 1977. 3. Collins, J. A.: Does a Relationship Exist between Massive Blood Transfusions and the Adult Respiratory Syndrome? Vox Sang., 32:313, 1977. 4. Collins, J. A., James, P. M., Bredenberg, C. E., et al.: The Relationship Between Transfusion and Hypoxemia in Combat Casualties. Ann. Surg., 188:513, 1978. 5. Donham, R. T.: Rationale and Indications for Microfiltration of Blood in Emergency Medicine. Med. Instrum., 11:344, 1977. 6. Moseley, R. V. and Doty, D. B.: Death Associated with Multiple Pulmonary Emboli Soon After Battle Injury. Ann. Surg., 171:336, 1970. 7. National Heart and Lung Institute's Blood Resource StudiesSummary Report. DHEW Publication No. (NIH)73-416. June 30, 1972. DHEW, Bethesda, Maryland p. 27. 8. Rangno, R. E.: The Rationale of Antibiotic Prophylaxis in Total Hip Replacement Arthroplasty. Clin. Orthop., 96:206, 1973. 9. Reul, G. J., Greenberg, S. D., Lefrak, E. A., et al.: Prevention of Post-traumatic Pulmonary Insufficiency. Arch. Surg., 106: 386, 1973. 10. Reul, G. J., Beall, A. C. and Greenberg, S. D.: Protection of the Pulmonary Microvasculature by Fine Screen Blood Filtration. Chest, 66:4, 1974. 11. Shulman, N. R., Weinrach, R. S., Libre, E. P. and Andrews, H. L.: The Role of the Reticuloendothelial System in the
Pathogenesis of Idiopathic Thrombocytopenic Purpura. Trans. Assoc. Am. Phys., 78:374, 1965. 12. Solis, R. T. and Gibbs, M. B.: Microaggregates in Stored Blood: Formation and Removal. In Chaplin, H., Jaffe, E. R., Lenfant, C. and Valeri, C. R. (eds.) Preservation of Red Blood Cells. Sponsored by Committee on Red Blood Cell Preservation, Division of Medical Sciences, National Research Council, June 5-6, 1972. National Academy of Sciences, Washington, D.C. p. 309. 13. Takaori, M., Nakajo, N. and Ishii, T.: Changes of Pulmonary Function Following Transfusion of Stored Blood. Transfusion, 17:615, 1977. 14. Virgilio, R. W., Smith, D. E., Rice, C. L., et al.: To Filter or not to Filter (Abstract). Inten. Care Med., 3:144, 1977.
D ATA FROM MILITARY6 and civilian9 1" trauma studies suggest that when transfused in large quantities, microaggregates play a role in the development of the adult respiratory distress syndrome. Furthermore, Solis and Gibbs12 have postulated that infusion of microaggregates might produce a blockade of the reticuloendothelial system and thus contribute to the bleeding and infection seen after massive blood transfusion. Few studies have evaluated these parameters in patients receiving low volume elective transfusions. To assess the in vivo effect of microaggregate blood
*Department of Internal
Medicine. t Department of Anesthesiology. t Department of Orthopaedics. Presented in part at the Annual Meeting of the American Association of Blood Banks, November 4-9, 1978, New Orleans,
Louisiana. Supported in part by National Research Service Award 5 T32 HL07080 USPHS, (Dr. Snyder) and a grant from Bentley Laboratories, Inc. Reprint requests: Edward L. Snyder. M.D., Yale-New Haven Hospital, 789 Howard Avenue, New Haven, Connecticut 06504.
From the Departments of Internal Medicine, Anesthesiology, and Orthopaedics, Montefiore Hospital and Medical Center, Bronx, New York
filtration (MABF) on pulmonary function, hemostatic function, and incidence of infection, we designed a prospective randomized study on patients undergoing elective total hip replacement.
Materials and Methods Patient Selection Criteria From June 1977 through July 1978, using a table of random numbers, 40 patients undergoing elective total hip replacement for primary or secondary osteoarthritis were assigned to one of two filter groups (Table 1). Patients paired with an even number (SF group; n = 20) received all blood transfusions through a large pore 260,u standard filter (Saftifilter 834-30, Cutter Laboratories, Berkeley, CA). The other patients, matched with an odd number, (MF group; n = 20) received blood infused through a 20,u microaggregate blood filter (PFF-100, Bentley Laboratories, Irvine, CA). To maintain uniformity between the two patient groups the following criteria were imposed: 1) Age: All patients were over 40 years of age. 2) Surgical history: All patients were scheduled for elective total hip replacement for either primary degenerative osteoarthritis or osteoarthritis secondary to previous hip surgery or trauma. 3) Medical history: Patients were free of clinically detectable renal, cardiovascular, pulmonary, hematologic, or systemic disease. Patients were excluded from the protocol if any of the following abnormalities were present: Renal: History of acute or chronic renal disease, serum creatinine over 1.3 mg/dl. Cardiovascular: History of right or left sided congestive heart failure, angina pectoris, recent cere-
0003-4932/79/0700/0075 $00.75 C) J. B. Lippincott Company
75
Ann. Surg.
SNYDER AND OTHERS
76 TABLE 1. Clinical Material
Patients Mean age (range) Sex (M/F) Mean transfusion (range)
MF-20,u Filter
SF-260,u Filter
20 69 (40-86) 3/17 4.6 (2-9)
20 63 (40-81) 3/17 4.0 (2-7)
brovascular accident, clinical evidence of extensive peripheral vascular disease, EKG evidence of myocardial ischemia or acute cardiac arrhythmia, radiographic evidence of cardiomegaly, systolic hypertension over 180 mmHg and diastolic hypertension over 106 mmHg. Pulmonary: History of obstructive or restrictive lung disease, chronic bronchitis, use of over one pack of cigarettes per day, abnormal chest radiograph, arterial blood gas on room air (FiO2-.21) showing a Paco2 over 42 mmHg and a Pao2 less than 70 mmHg. Hematologic: History of chronic bleeding diathesis, abnormal preoperative platelet count or prothrombin time. Systemic: Presence of any systemic illness i.e., sickle cell anemia, rheumatoid arthritis, or carcinoma.
Parameters Studied
Evaluation of MABF in these surgical patients included: 1) Hematologic (preoperative and two hours postoperative): hematocrit, hemoglobin, white blood count, plasma hemoglobin. 2) Clinical chemistry (preoperative and two hours postoperative): serum sodium, potassium, albumin, globulin. 3) Hemostasis (preoperative and two hours postoperative): platelet count, prothrombin time; volume of blood collected from the postoperative wound drain (1-72 hours postoperatively). 4) Pulmonary (preoperative, intraoperative, two hours
Protocol
Informed consent was obtained from all patients in the study in accordance with the recommendations and approval of the Human Subjects Committee of Montefiore Hospital and Medical Center. Baseline preoperative clinical laboratory studies were drawn prior to surgery (Table 2). Preoperative arterial blood gases (PREOP) were obtained immediately prior to intubation while the patient was awake and breathing room air (FiO2-.21). After induction and maintenance of anesthesia using a neurolept technique the patient was placed on a respirator with FiO2 of .33. Thirty minutes after intubation, during the initial surgical skin incision, a blood gas (SI) was obtained through an indwelling radial artery catheter previously inserted for routine intraoperative patient monitoring. Additional blood gases were subsequently obtained after each unit of blood and 15 minutes after each of the two parts of the Charnley hip prosthesis were cemented into place using methylmethacrylate bone cement (MMA- 1, MMA-2). During surgery, if the FiO2 was altered for any reason, it was reset to .33 for 20 minutes prior = 20)
± SEM
Preoperative*
Hematocrit (%) Hemoglobin (g/dl) W.B.C. (x1011/) Platelets (x109/l) Plasma hemoglobin (mg/dl) Sodium (mEq/l) Potassium (mEq/l) Albumin (g/dl) Globulin (g/dl) Prothrombin time (sec)t *
P > O.OS (N.S-)-
20,u-MF 38.5 13.0 7.3 208.5 4.5 141 4.3 4.3 3.0
+ ± ± ± ± ± ± 10
0.9 0.4 0.5 12.4 0.5 0.6 0.1 0.1 0.1
July 1979
postoperative, 48 hours postoperative): arterial pH, Po2, Pco2. 5) Infection: postoperatively until discharge patients were monitored for development of infection using the following criteria: a) Urinary tract infection: Pyuria on urinanalysis with clean catch urine samples sent for culture reported as having over 100,000 bacterial colonies for females, or over 10,000 colonies for males. b) Septicemia: Positive blood cultures. c) Operative wound infection: clinical signs of infection and/or inflammation with positive bacterial cultures. d) Pulmonary infection: clinical and/or radiographic evidence of consolidation or infiltration with positive sputum gram stain or culture.
TABLE 2. Clinical Laboratory Tests (n
Parameter
*
2H Postoperative*
20,-MF
260,u-SF 37.8 12.8 7.7 228.6 5.0 141 4.2 4.1 3.2
± ± ± ± ± ± ±
33.5 11.4 12.2 148.3 6.7 136 3.7 3.5 2.0
1.3 0.4 0.6 14.8 0.7 0.8 0.1 0.1 0.1
11
10
t Normal control
± ± ± ± ± ± ±
=
10 seconds.
1.0 0.4 1.1 13.6 0.7 1.1 0.1 0.1 0.1
2604-SF 35.6 12.0 15.9 163.6 6.4 136 3.7 3.5 2.3
± ± ± ± ± ± ± ± ±
11
1.1 0.4 1.6 18.7 0.7 0.9 0.1 0.1 0.1
Vol. 190.oNO.
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77
TABLE 3. Preoperative and Postoperative Blood Gas Results (FiO2-.21)
MF-20i. (n = 20)
SF-260,a Filter*
(n = 20) 2H-Post
Preop 7.41 + .01 36.5 + 1.2 80.4 + 2.5 *
Filter* + S.E.M.
7.39 37.5 71.1
--
+ +
(n = 13) 48H-Post
.01 0.9 3.0
7.45 32.3 73.5
+ + +
(n = 20)
Preop
.01 0.8 3.2
pHa
7.40 + .01 38.5 -+- 0.8 80.2 + 2.3
Paco2 Pao2
+
S.E.M.
(n = 20) 2H-Post 7.36 40.2 71.5
+ -++
.01 1.0 2.0
(n = 14) 48H-Post 7.44 33.6 75.0
+ + +
.01 0.9 2.4
p > 0.05 (N.S.)
to resampling. A final intraoperative blood gas (SC) obtained at the time of skin closure (FiO2-.33)
was
following completion of the procedure. Two hours postoperatively, the various blood tests listed in Table 2, and another blood gas (2H-POST) were obtained (FiO2-.21). For most patients a blood gas was also obtained 48 hours postoperatively (48H-POST) via a single radial artery puncture with the patient breathing room air (FiO2-.21). All blood drainage collected via a Hemovac wound drain (Snyder Manufacturing Company, New Philadelphia, Ohio) was measured. The drain was routinely left indwelling up to 72 hours. As part of routine care all patients received aminoglycoside antibiotics intraoperatively and for 24-48 hours postoperatively. All patients received intensive postoperative pulmonary toilette, and were encouraged to begin early ambulation. Urine cultures were collected from all patients who developed a fever during the first two postoperative days. Subsequent cultures were obtained if the patient again became febrile, or developed clinical symptoms of urinary tract infection. Blood cultures were drawn on patients with either a high postoperative fever or with a new or persisting fever lasting over 24-48 hours. Cultures of the operative wound were taken from patients with clinical signs of infection such as delayed wound closure associated with erythema and serous drainage. Pulmonary status was clinically monitored each day. Chest radiographs and sputum cultures were obtained from patients with postoperative fever and cough in whom a pneumonic process was suspected. This type of evaluation was initiated whenever a clinical diagnosis
of pneumonia was considered in a patient, regardless of the amount of time that had elapsed since the day of surgery. All transfused bloods were at least 12 days old. Collected data was analyzed using a parametric twotailed Student's t-test for independent sets, and a nonparametric two-tailed Wilcoxson rank-sum test. The level of statistical significance used was p < 0.05. Results Evaluation of the clinical material is shown in Table 1. The comparison of clinical laboratory tests was made preoperatively to document additional similarity between the two filter groups, and postoperatively to exclude any harmful effects from the microaggregate filtration of blood in the amounts used in the study (Table 2). As seen there were no statistically significant differences between the two groups of surgical patients. Similarity in the preoperative and postoperative plasma hemoglobins for the two groups excluded clinically significant MABF-induced hemolysis. Arterial blood gas results (Table 3) showed that on room air (FiO2-.21) preoperatively and 2 hours postoperatively there were no differences (p > 0.05) between the two groups for either arterial pH, Pco2 or Po2. Blood gases sampled 48 hours postoperatively also failed to show any variation between the two sample populations. Similarly, arterial blood gases taken intraoperatively (Table 4) with patients intubated (FiO2-.33) showed no difference between samples taken at the start of surgery (SI) and those obtained at the end of the operation during skin closure (SC) after all blood transfusions had been given. Blood gases
TABLE 4. Intraoperative Blood Gas Results (FiO2-.33)
MF-20,u Filter (n
=
20)*
+
SF-260,u. Filter (n = 20)*
S.E.M.
SI
MMA-1
MMA-2
SC
7.43 + .01 33.7 ± 1.2 115.7 ± 4.2
7.41 + .01 33.8 ± 1.3 115.7 + 5.6
7.41 + .01 34.9 ± 1.2 108 ± 6.0
7.41 + .01 35.1 ± 1.2 114.6 ± 6.2
*
p > 0.05 (N.S.).
pHa
PacO2 Pao2
+
S.E.M.
SI
MMA-1
MMA-2
SC
7.41 + .01 35.9 ± 0.9 121.3 ± 6.0
7.41 ± .01 33.7 ± 1.2 112.6 ± 5.5
7.41 ± .01 34.5 ± 1.3 112.2 ± 6.2
7.40 ± .01 35.3 ± 1.2 119.1 ± 6.7
Ann.
SNYDER AND OTHERS
78 TABLE 5. Postoperative Bleeding
MF-20,u Filter* (n =20) 644
54 ml
SF-260,u Filter* (n 621
20) 69 ml
* (p > 0.05) (N.S.).
obtained five minutes after the hip prothesis was cemented into place (MMA- 1, MMA-2) were unchanged from the values obtained during skin incision (SI). The volume of fluid intake and output was monitored for 48 hours postoperatively and showed no statistically significant differences (p > 0.05) between the two groups. None of the patients in either filter group developed clinical signs of respiratory distress postoperatively. Patient tendency to hemorrhage (Table 5) evaluated by measurement of the total drainage from the operative wound site during the 72 hours that the wound drain remained indwelling, showed that the total volumes collected from both filter groups were comparable. Routine evaluation of all patients in both filter groups revealed no evidence of preoperative infection. All patients entered into the study were afebrile, had chest radiographs which were negative for acute infiltration, urinanalyses which were negative for active urinary tract infection, and white blood counts which were within the normal limits for the laboratory. Postoperatively all patients became febrile but defervesced within 72 hours unless a bacterial infection was found (Table 6). These transient febrile episodes were attributed to an inflammatory response to surgery. Postoperative urine cultures were obtained from all 40 patients in both groups during the first 24-48 hours and subsequently as described in the protocol. At the end of the study only six infections had been documented in the 20, filter group and four infections verified in the 260, filter group. Exclusion of those patients who had indwelling bladder catheters reduced the incidence of urinary tract infection to only two patients in each filter group. No patient developed a bacteriologically proven deep wound infection during the course of the study, and in only one patient was the diagnosis considered. Although a superficial wound infection was suspected in 11 of the 40 study patients, only seven of the 11 patients evaluated had positive bacterial cultures. Staphylococcus epidermidis was the predominant organism cultured from the skin of three patients in the MF group and three of four patients in the SF group (Table 6). Blood cultures were obtained from 35% of the patients in the 20,u MF group and 3 0% of the patients in the 260, SF group. All of the cultures were sterile.
Surg. July 1979 *
Postoperatively none of the patients in either group developed respiratory distress. During the course of the study chest radiographs were ordered for seven patients in the microaggregate filter group and six patients in the standard filter group. Although atelectasis was reported on several of the postoperative films, none of the radiographs disclosed any evidence of acute infiltration or consolidation. Sputum cultures on the patients studied were reported as "'normal flora." Discussion For the parameters investigated in our study no evidence was found that any benefit accrued to patients who received microaggregate filtered blood in the amounts used. We evaluated two sets of blood gas determinations, one set pre- and postoperatively while the patients were spontaneously breathing room air (FiO2-.21), and the second set intraoperatively during anesthesia (FiO2-.33). This provided a method of double checking the results since blood gases collected during spontaneous respiration could have been influenced by hypoventilation either from preoperative sedation or from postoperative incisional pain. No discrepancies between the two sets of data were found. No reduction in postoperative hemorrhage was found in those patients receiving microaggregate filtered blood. For infections the numbers were too small to permit statistically significant conclusions.8 Rather we were interested in trends which might imply a protective effect attributable to use of microaggregate filters. No such trends were seen. Although a blockade of the reticuloendothelial system may be involved in the increased bleeding and infection reported after massive transfusions, we could not document that either of these clinical findings occurred after the transfusion of up to five units of blood in our patients. TABLE 6. Postoperative Infection
MF-20,u Filter (n = 20)
Parameter Fever (+ 38°) Septicemia (blood cultures) Deep wound infection Superficial wound infection Pneumonia Urinary tract infection total without catheter
SF-260,u Filter (n = 20)
Patients Evaluated
Patients Positive
Patients Evaluated
20
20
20
20
7
0
6
0
1
0
0
0
5 7
3* 0
6 6
4** 0
20 7
6 2t
20 8
Patients Positive
4
2t
*Staphylococcus epidermidis -3. **Staphylococcus epidermidis -3; Proteus sp. -1. tProteus sp. -2. tPseudomonas aeruginosa -2.
Vol. 190 * No. I
MICROAGGREGATE BLOOD FILTRATION
The number of microaggregates infused with four-five units of blood (3-3.5 x 108) may have been insufficient to affect the reticuloendothelial system.11 Alternatively, additional factors not detectable in our patients such as sustained hypotension, disseminated intravascular coagulation or hypovolemic shock may be playing a major causative role in the development of the bleeding and infection seen in massively transfused trauma patients. Our study documented a lack of changes in arterial blood gases in the SF group up to 48 hours posttransfusion by which time significant changes in pulmonary gas exchange should have become detectable. Sensitive tests of pulmonary function have been able to detect some alterations in gas exchange after low volume transfusions, however, these changes have not been found consistently. For patients transfused with less than 3000 ml of blood, Takaori et al.13 reported some adverse changes in pulmonary dead space (VD/ VT) but no alterations in pulmonary shunting (Qs/Qt). Barrett et al.1 found abnormalities in Qs/Qt in patients receiving several units of blood through a standard 170,t filter, but none in patients receiving microaggregate filtered blood. Virgilio et al.14 however, reported finding no alterations in pulmonary function tests for 20 patients receiving an average of six-seven units of blood through a 170,u filter. None of the patients described in these three studies developed any clinical signs of respiratory distress. The relationship between transfusion and subsequent hypoxemia was recently examined in a retrospective analysis of Vietnam combat casualties. Collins' group4 concluded that differences in Pao2 noted in soldiers studied were more likely related to the type and the magnitude of injury sustained than the amount of blood
transfused. Of the over 6 million units of blood estimated to be transfused yearly in the United States,7 the majority of patients receive less than four units. Since patients receiving low volume transfusions through standard pore filters are clinically asymptomatic with no evidence of hypoxemia, there seems to be little scientific justification for the proposal made by some authors5 13 that MABF should be used routinely regardless of the volume of blood infused. Even the data reported by Reul9'10 showing a need for MABF in massively transfused patients has been questioned, due to differences between the two groups of patients compared.2'3 Economic factors also enter into the decision to use MABF for all transfusions. At present, a MABF-administration set costs several dollars more than a standard blood administration set.
79
It is possible that while the healthy lung can compensate for microaggregate emboli, a diseased lung cannot. Controlled studies evaluating the effect of low volume transfusions in patients with compromised pulmonary function are lacking; routine use of MABF in such patients may be of value. Based on our study of arterial blood gases, bleeding tendency, and infection rate, we conclude that routine microaggregate blood filtration of up to five units of blood is not required.
Acknowledgments The authors wish to thank Mrs. R. Condon for excellent secretarial assistance.
References 1. Barrett, J., Tahir, A. H. and Litwin, M. S.: Increased Pulmonary Arteriovenous Shunting in Humans Following Blood Transfusion. Arch. Surg., 113:947, 1978. 2. Bredenberg, C. E.: Does a Relationship exist between Massive Blood Transfusions and the Adult Respiratory Distress Syndrome? Vox Sang., 32:311, 1977. 3. Collins, J. A.: Does a Relationship Exist between Massive Blood Transfusions and the Adult Respiratory Syndrome? Vox Sang., 32:313, 1977. 4. Collins, J. A., James, P. M., Bredenberg, C. E., et al.: The Relationship Between Transfusion and Hypoxemia in Combat Casualties. Ann. Surg., 188:513, 1978. 5. Donham, R. T.: Rationale and Indications for Microfiltration of Blood in Emergency Medicine. Med. Instrum., 11:344, 1977. 6. Moseley, R. V. and Doty, D. B.: Death Associated with Multiple Pulmonary Emboli Soon After Battle Injury. Ann. Surg., 171:336, 1970. 7. National Heart and Lung Institute's Blood Resource StudiesSummary Report. DHEW Publication No. (NIH)73-416. June 30, 1972. DHEW, Bethesda, Maryland p. 27. 8. Rangno, R. E.: The Rationale of Antibiotic Prophylaxis in Total Hip Replacement Arthroplasty. Clin. Orthop., 96:206, 1973. 9. Reul, G. J., Greenberg, S. D., Lefrak, E. A., et al.: Prevention of Post-traumatic Pulmonary Insufficiency. Arch. Surg., 106: 386, 1973. 10. Reul, G. J., Beall, A. C. and Greenberg, S. D.: Protection of the Pulmonary Microvasculature by Fine Screen Blood Filtration. Chest, 66:4, 1974. 11. Shulman, N. R., Weinrach, R. S., Libre, E. P. and Andrews, H. L.: The Role of the Reticuloendothelial System in the
Pathogenesis of Idiopathic Thrombocytopenic Purpura. Trans. Assoc. Am. Phys., 78:374, 1965. 12. Solis, R. T. and Gibbs, M. B.: Microaggregates in Stored Blood: Formation and Removal. In Chaplin, H., Jaffe, E. R., Lenfant, C. and Valeri, C. R. (eds.) Preservation of Red Blood Cells. Sponsored by Committee on Red Blood Cell Preservation, Division of Medical Sciences, National Research Council, June 5-6, 1972. National Academy of Sciences, Washington, D.C. p. 309. 13. Takaori, M., Nakajo, N. and Ishii, T.: Changes of Pulmonary Function Following Transfusion of Stored Blood. Transfusion, 17:615, 1977. 14. Virgilio, R. W., Smith, D. E., Rice, C. L., et al.: To Filter or not to Filter (Abstract). Inten. Care Med., 3:144, 1977.
