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Effect of Intraoperative Blood Loss on the Serum Level of Cefazolin in Patients Managed with Total Hip Arthroplasty. A Prospective, Controlled Study*

MAJOR JEFFREY J. METER, , MAJOR DAVID W. POLLY, JR., , LIEUTENANT COLONEL RALF P. BRUECKNER, , MAJOR JOACHIM J. TENUTA, , UNITED STATES ARMY, LYNN ASPLUND, R.N. and WILLIAM J. HOPKINSON, M.D., WASHINGTON, D.C.

Investigation performed at Walter Reed Army Medical Center, Washington, D.C.

	Abstract

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The effect of intraoperative blood loss on serum levels of cefazolin in patients being managed with total hip arthroplasty was studied. Eighteen patients, thirteen men and five women, with a mean age of sixty-five years (range, forty to eighty-five years) were enrolled in the study. Fifteen had a primary total hip arthroplasty and three, a revision. Each patient served as his or her own control. Baseline clearance of cefazolin was determined at a minimum of forty-eight hours before the operation. Each patient received one gram of cefazolin intravenously. Serial serum concentrations were determined from specimens drawn at zero, five, ten, twenty, thirty, sixty, 120, 240, and 300 minutes after administration. Fifteen minutes before the skin incision was made, each patient again received one gram of cefazolin intravenously. Serum samples were collected at the same time-intervals, and the serum levels of cefazolin were determined with use of capillary electrophoresis. Data regarding intraoperative blood loss as well as replacement of fluid and blood were recorded. The administration of the antibiotic, retrieval of the serum samples, and estimation of the blood loss were performed by the same person in the same manner for all patients. The preoperative and intraoperative creatinine clearances (mean and standard deviation), estimated with use of the formula of Cockcroft and Gault, were 62.06 ± 21.28 and 74.02 ± 24.75 milliliters per minute, respectively. The amount of intraoperative blood loss averaged 1137 ± 436 milliliters (range, 675 to 2437 milliliters). The preoperative and intraoperative cefazolin clearances averaged 0.49 ± 0.21 and 0.52 ± 0.30 milliliter per minute per kilogram, respectively. During joint replacement, the commonly accepted interval between doses of cefazolin is four hours. In the present study, the serum level of cefazolin at four hours was forty-five micrograms per milliliter. This corresponds to an osseous concentration that well exceeds the minimum inhibitory concentration for Staphylococcus aureus, which is 0.5 microgram per milliliter. This study suggests that, with blood losses of less than 2000 milliliters, it is not necessary to administer cefazolin at intraoperative intervals of less than four hours in order to maintain a concentration of antibiotics that is higher than the minimum inhibitory concentration for the most common infecting organisms.

	Introduction

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Deep wound infection is a well known and potentially devastating complication of total joint arthroplasty. Early reports of the prevalence of deep infection following total hip arthroplasty were disappointing. Charnley and Eftekhar reported that 8.9 per cent of 190 patients had such an infection in Britain between 1959 and 1961. Attempts to reduce the rate of infection have centered around the use of laminar airflow systems, body-exhaust systems, and perioperative antibiotics. Antibiotic prophylaxis has been credited with reducing the rate of infection after total hip arthroplasty to less than 1 per cent^{5,6,11,16,17,22}.

The goal of antibiotic prophylaxis is to prevent infection by maintaining adequate serum levels of the antibiotic during the operative and perioperative periods, when the presumed risk of infection is greatest^7,15. There is no consensus as to what constitutes adequate serum levels of antibiotics; however, the minimum inhibitory osseous concentration of cefazolin for the most common infecting organisms (Staphylococcus and Streptococcus species and some gram-negative organisms) is 0.5 microgram per milliliter¹⁸.

It has been commonly accepted that intraoperative blood loss results in more rapid clearance of antibiotics from the body. The current practice of many surgeons is to shorten the interval between doses, in order to maintain adequate serum levels, when there is a major loss of blood. There are currently little or no data to support this practice.

The purpose of the present study was to determine what effect, if any, intraoperative blood loss has on serum levels of antibiotics, in order to determine if the dose or the interval between the doses should be adjusted during operations associated with major loss of blood. Cefazolin is well suited for this study. It is a widely used drug, excreted by the kidneys, that has been studied extensively and found to be efficacious for the prevention of infection following total joint arthroplasty¹¹. There is good evidence that anesthetic agents do not affect the pharmacokinetics of cephalosporins¹⁹. To our knowledge, we are the first to perform a prospective, controlled study of the pharmacokinetic effect of intraoperative blood loss on the serum level of cefazolin in patients managed with total hip arthroplasty.

	Materials and Methods

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Patients
Eighteen patients, ranging in age from forty to eighty-five years (mean, sixty-five years), who were scheduled for elective total hip arthroplasty were entered into this study. Informed written consent was obtained from all patients. The study was approved by the local institutional review board. There were thirteen men and five women, who weighed an average of eighty kilograms (range, thirty-one to 104 kilograms). Fifteen patients had a primary total hip arthroplasty, and three had a revision procedure. Two patients had rheumatoid arthritis, and the remainder had osteoarthrosis.

Experimental Protocol
All patients had a routine preoperative evaluation, including determination of creatinine clearance with use of the formula of Cockcroft and Gault. The preoperative pharmacokinetics of cefazolin were evaluated in each patient during the week before the operation, with a minimum forty-eight-hour interval between this test and the operation. Cefazolin (one gram in ten milliliters of sterile water) was injected intravenously during a five-minute period, after which the line was flushed with normal saline solution. Zero, five, ten, twenty, thirty, sixty, 120, 240, and 300 minutes later, blood was obtained from a site separate from the site where the antibiotic had been administered. These specimens were centrifuged, and the serum was removed and stored at -20 degrees Celsius until the assay was performed for determination of the cefazolin level.

On induction of anesthesia (within one hour before the operative incision), each patient received one gram of cefazolin intravenously, in the same manner as preoperatively. Blood was drawn and stored as described. Data regarding intraoperative blood loss, administration of fluid, and transfusion of blood were recorded throughout each procedure by the same one of us (L. A.), in the same manner for each patient. In order to estimate blood loss closely, intraoperative suction drainage and irrigation fluids were measured and the sponges were weighed. Blood lost through drainage (closed system, low-pressure suction drainage), administration of fluid, and blood transfusion were also recorded postoperatively, until five hours after the initiation of the operation. All of the operations were performed by the same one of us (W. J. H.).

Cefazolin Assay
The levels of cefazolin in serum were determined with a Quanta-4000 capillary electrophoresis system (Waters Associates, Milford, Massachusetts), equipped with a 254-nanometer ultraviolet detector. The evaluations were performed with a fifty-micrometer by sixty-centimeter fused silica capillary, maintained at 20,000 volts. All injections were hydrostatic. The electrolyte solution was a sodium bicarbonate buffer (pH 10). Twenty-five microliters of water and 250 microliters of acetonitrile were added to 225 microliters of sample. The mixture was vortexed and centrifuged at 3000 revolutions per minute for ten minutes to precipitate proteins. The samples were filtered through 0.45-micrometer filters and injected onto the capillary column. Minimum assay sensitivity was 5.00 micrograms per milliliter. Unknown values were calculated with use of a five-point standard curve with r² > 0.9998 and an interday coefficient of variability of 0.78 per cent at 13.3 micrograms per milliliter.

Pharmacokinetics
The cefazolin clearance and elimination half-life were determined for each subject both before the operation (the baseline value) and during the operation. A non-compartmental analysis was first used to obtain initial estimates of these parameters⁸. A one or two-compartment open model with zero-order input as well as first-order elimination was then fit to the plasma concentration-time data to give final estimates of these parameters¹².

Statistical Analysis
The preoperative pharmacokinetic parameters (creatinine clearance, cefazolin clearance, and cefazolin half-life) were compared with the intraoperative parameters with use of the Wilcoxon signed-rank test. To determine if there was a difference between the cefazolin concentrations before and during the operation, data were logarithmically transformed to satisfy assumptions of homogeneity of variance and compared with repeated-measures analysis of variance. Linear regression analysis was performed to determine the relationship between blood loss and a change in the pharmacokinetic parameters from the baseline value. Once the pharmacokinetic model was developed, a model describing the operative blood loss was added in order to predict the effect of blood loss of as much as five liters. With use of values from the literature for the pharmacokinetics of three additional antibiotics (cefuroxime³, gentamicin²⁰, and vancomycin⁹), the effect of operative blood loss on their concentrations was estimated.

	Results

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All patients tolerated the operation well; there were no perioperative complications. After a mean duration of follow-up of 2.4 years (range, five to twenty-nine months), there were no infections at the operative site in any patient.

The mean operative time was 144 minutes (range, ninety-four to 240 minutes). The patients lost a mean (and standard deviation) of 1137 ± 436 milliliters of blood (range, 675 to 2437 milliliters of blood): 1022 milliliters intraoperatively and 115 milliliters postoperatively (measured until five hours after the start of the operation). Revision procedures were associated with a mean loss of 1715 milliliters of blood. The patients received a mean of 3318 milliliters of fluid (crystalloid, colloid, and blood) intraoperatively and 212 milliliters postoperatively (measured until five hours after the initiation of the operation). The serum creatinine level (mean and standard deviation) was 1.12 ± 0.29 milligrams per deciliter (99 ± 26 micromoles per liter) preoperatively and 0.94 ± 0.30 milligrams per deciliter (83 ± 27 micromoles per liter) intraoperatively. The mean creatinine clearance increased slightly, from 62.06 ± 21.28 milliliters per minute during the preoperative evaluation to 74.02 ± 24.75 milliliters per minute intraoperatively (p = 0.0006).

Pharmacokinetics
Comparison of the mean preoperative clearance and half-life of cefazolin with the intraoperative values for all patients combined showed no significant differences, with the numbers available. The mean cefazolin clearance preoperatively and intraoperatively for all patients was 0.49 ± 0.21 and 0.52 ± 0.30 milliliter per minute per kilogram (p = 0.17), and the mean half-life was 2.6 ± 1.0 and 2.4 ± 1.1 hours, respectively. Curves that compared the serum concentration of cefazolin at each time-point preoperatively and intraoperatively were not significantly different (p = 0.10) (Fig. 1).

View larger version (20K): [in this window] [in a new window]   Curves comparing the preoperative and intraoperative serum concentrations of cefazolin at each time-point. At five hours, both curves are still well above the minimum inhibitory serum concentration for Staphylococcus aureus, which is five micrograms per milliliter, corresponding to an estimated osseous level of 0.5 microgram per milliliter.

	Discussion

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Antibiotic prophylaxis for patients being managed with total hip arthroplasty reduces the prevalence of postoperative infection^{5,6,11,16,17,22}. Maintenance of an adequate level of the antibiotic from the time of the incision through that of the closure of the skin is thought to be critical to prophylaxis^7,15. In an effort to maintain an adequate level of the antibiotic, many surgeons shorten the interval between doses when there is major loss of blood. The purpose of the present study was to determine the effect of intraoperative blood loss on serum levels of antibiotics and whether the interval between doses needs to be shortened when there is major loss of blood. While the serum concentration of antibiotics required to prevent infection after total joint arthroplasty is unknown, our prospective, controlled study showed that loss of less than 2000 milliliters of blood has no clinical effect on serum levels of cefazolin and does not necessitate shortening the interval between doses in order to maintain serum levels that well exceed the minimum inhibitory concentration.

The effect of the complexity of a total hip arthroplasty on the rate of deep wound infection was evaluated by Schutzer and Harris. Procedures were defined as complex when they were revisions or when they involved the use of autogenous or allogeneic graft. Their study showed that more complex procedures were associated with much higher rates of infection. However, the duration of the procedure and the amount of blood loss were not evaluated separately. Guglielmo et al. evaluated the alteration of the pharmacokinetics of cefamandole due to blood loss in patients being managed with vascular procedures. A factor in that study that limits the application of its findings to orthopaedic procedures is that the aorta was cross-clamped, resulting in alterations in renal blood flow and drug clearance. Other studies have demonstrated that blood loss alters the pharmacokinetics of drugs that are primarily cleared by the kidneys: Shanks et al. showed a higher-than-predicted serum level of D-tubocurarine and Kloth et al. found a lower-than-predicted level of gentamicin within the perioperative period.

In a study of adults being managed with elective cardiac procedures, Sue et al. found that blood loss had a minimum effect on serum levels of cefazolin and that no alteration of the dosage interval was necessary. The mean blood loss in that study was 1123 milliliters, similar to that measured in our investigation. The serum half-life was 5.5 hours, compared with 2.4 hours in our study. Since cefazolin is renally excreted in an unaltered state, the increased half-life was a direct effect of the difference in creatinine clearance; in the study by Sue et al., the mean creatinine clearance was nearly half that in our study. Sue et al. did not perform pharmacokinetic modeling or include a non-operative control group as we did. We were able to compare the intraoperative cefazolin clearance with that in a well matched control (the same patient).

In 1993, Lopez-Sosa et al. reported that they had found no relationship between the serum half-life of cefazolin and blood loss during spinal arthrodesis in children. Again, they had neither performed pharmacokinetic modeling or analysis nor included a control group. Lopez-Sosa et al. recommended administration of cefazolin at two-hour intervals because the serum level of cefazolin at three hours was twelve micrograms per milliliter. However, the dose given in their series (12.5 milligrams per kilogram of body weight) is much lower than the usual dose (twenty-five to fifty milligrams per kilogram of body weight). Therefore, the necessity of administering doses at such short intervals is unclear.

In our study, the patients themselves acted as a control group. Pharmacokinetic analysis and modeling failed to show a difference between the baseline and intraoperative pharmacokinetics of cefazolin. The lack of effect of the blood loss on the drug levels in our study is most likely due to the relatively small amount of drug that was lost with the blood. As cefazolin does not penetrate red blood cells, loss of the drug is related to the intraoperative and postoperative loss of plasma rather than to the loss of blood. The amount of the drug that is lost over any period of time thus can be approximated by multiplying the drug concentration in the plasma by the volume of plasma that was lost. In the case of cefazolin, this amounts to a theoretical maximum loss of 131.7 milligrams. This was determined with the equation: 193 micrograms per milliliter (the peak serum cefazolin concentration at five minutes in this study) x 1137 milliliters (the mean blood loss in this study) x 0.60 (the reciprocal of the estimated hematocrit). This amount of cefazolin (131.7 milligrams) is less than 15 per cent of the administered dose (one gram). This theoretical maximum loss could occur only if all of the blood was lost at the time of the peak concentration of cefazolin. Thus, one would not expect clinically important decreases in drug concentrations in the elective setting of total hip arthroplasty. The effect on the serum level of cefazolin of massive exsanguinating hemorrhage due to trauma or another cause cannot be determined from this study.

During joint replacement, many surgeons administer cefazolin at four-hour intervals. In the present study, the serum level of cefazolin at four hours was forty-five micrograms per milliliter. Although, to our knowledge, no study has been performed to determine the ratio between serum and osseous levels of cefazolin, several studies^{4,18,21,25,26} have indicated that osseous levels of cefazolin are approximately 10 to 30 per cent of serum concentrations. Therefore, if the conservative value of 10 per cent is used, the osseous level of cefazolin at four hours would be at least four micrograms per milliliter. This level is much higher than the reported minimum inhibitory concentration of cefazolin (0.5 microgram per milliliter) for the usual infecting organisms (Staphylococcus and Streptococcus species and some gram-negative organisms)¹⁸.

Our data indicate that shortening of the interval between doses of cefazolin to less than four hours is not necessary in association with blood loss of less than 2000 milliliters. Although no clinical data were obtained, computer modeling with use of pharmokinetic values obtained from the literature^3,9,20 revealed that a blood loss of 2000 milliliters also would not be associated with a significant decrease in the concentrations of cefuroxime, gentamicin, or vancomycin (p = 0.255 to 0.259). We also used our modeling data to calculate the pharmacokinetics associated with blood loss of 5000 milliliters. With such a loss, the serum level of cefazolin at eight hours would be 5.0 micrograms per milliliter. This translates to an osseous level of 0.5 microgram per milliliter (assuming a 10 per cent ratio), which is still at the minimum inhibitory concentration. Therefore, a one-gram preoperative dose of cefazolin will maintain the serum, and presumably the osseous, level of cefazolin at well greater than the minimum inhibitory concentration for as long as eight hours and in association with a blood loss of as much as 5000 milliliters.

NOTE: The authors thank Ms. Robin Howard, Biostatistics, and Maged Abdelrahim, Chemistry Division, Department of Clinical Investigation, Walter Reed Army Medical Center, for their assistance with this project.

	Footnotes

 
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Funds were received in total or partial support of the research or clinical study presented in this article. The funding source was the Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, D.C.

Orthopaedic Surgery Service (J. J. M.; D. W. P., Jr.; J. J. T.; and L. A.) and Experimental Therapeutics (R. P. B.), Walter Reed Army Medical Center, Washington, D.C. 20307-5001. Please address requests for reprints to Major Polly.

Department of Orthopaedic Surgery, Loyola University Medical Center, 21605 First Avenue, Maywood, Illinois 60153.

	References

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1. Charnley, J., and |and |Eftekhar, N.: Postoperative infection in total prosthetic replacement arthroplasty of the hip-joint. With special reference to the bacterial content of the air of the operating room. British J. Surg., 56: 641-649, 1969.[Medline]
2. Cockcroft, D. W., and |and |Gault, M. H.: Prediction of creatinine clearance from serum creatinine. Nephron, 16: 31-41, 1976.[Medline]
3. Colaizzi, P. A.; Goodwin, S. D.; Poynor, W. J.; Karnes, H. T.; and |and |Polk, R. E.: Single-dose pharmacokinetics of cefuroxime and cefamandole in healthy subjects. Clin. Pharm., 6: 894-899, 1987.[Medline]
4. Cunha, B. A.; Gossling, H. R.; Pasternak, H. S.; Nightingale, C. H.; and |and |Quintiliani, R.: The penetration characteristics of cefazolin, cephalothin, and cephradine into bone in patients undergoing total hip replacement. J. Bone and Joint Surg., 59-A: 856-859, Oct. 1977.[Abstract/Free Full Text]
5. Doyon, F.; Evrard, J.; Mazas, F.; and |and |Hill, C.: Long-term results of prophylactic cefazolin versus placebo in total hip replacement [letter]. Lancet, 1: 860, 1987.
6. Fitzgerald, R. H., Jr.: Total hip arthroplasty sepsis. Prevention and diagnosis. Orthop. Clin. North America, 23: 259-264, 1992.[Medline]
7. Fitzgerald, R. H., Jr., and |and |Thompson, R. L.: Current concepts review. Cephalosporin antibiotics in the prevention and treatment of musculoskeletal sepsis. J. Bone and Joint Surg., 65-A: 1201-1205, Oct. 1983.[Free Full Text]
8. Gibaldi, M., and Perrier, D.: Pharmacokinetics. Ed. 2. New York, Marcel Dekker, 1982.
9. Golper, T. A.; Noonan, H. M.; Elzinga, L.; Gilbert, D.; Brummett, R.; Anderson, J. L.; and |and |Bennett, W. M.: Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects. Clin. Pharmacol. and Therapeut., 43: 565-570, 1988.
10. Guglielmo, B. J.; Salazar, T. A.; Rodondi, L. C.; Carver, M.; Goldstone, J.; and |and |Stoney, R. J.: Altered pharmacokinetics of antibiotics during vascular surgery. Am. J. Surg., 157: 410-412, 1989.[Medline]
11. Hill, C.; Flamant, R.; Mazas, F.; and |and |Evrard, J.: Prophylactic cefazolin versus placebo in total hip replacement. Report of a multicentre double-blind randomised trial. Lancet, 1: 795-79, 1981.[Medline]
12. Holford, N.: MKMODEL, version 4. New Jersey, Biosoft, 1990.
13. Kloth, D. D.; Tegtmeier, B. R.; Kong, C.; Akahoshi, M. P.; Leach, S. H.; Beatty, J. D.; and |and |Zaia, J. A.: Altered gentamicin pharmacokinetics during the perioperative period. Clin. Pharm., 4: 182-185, 1985.[Medline]
14. Lopez-Sosa, F. H.; Polly, D.; Bowen, J. R.; Eppes, S. C.; Klein, J. D.; St. John, K. H.; and |and |Corddry, D. H.: Serum cefazolin levels during spinal fusion: effect of blood loss and duration of surgery. J. Spinal Disord., 6: 296-299, 1993.[Medline]
15. Mader, J. T., and |and |Cierny, G., III: The principles of the use of preventive antibiotics. Clin. Orthop., 190: 75-82, 1984.
16. Marotte, J. H.; Lord, G. A.; Blanchard, J. P.; Guillamon, J. L.; Samuel, P.; Servant, J. P.; and |and |Mercier, P. H.: Infection rate in total hip arthroplasty as a function of air cleanliness and antibiotic prophylaxis. 10-year experience with 2,384 cementless Lord madreporic prostheses. J. Arthroplasty, 2: 77-82, 1987.[Medline]
17. Mulier, J. C.; Vandepitte, J.; Stuyck, J.; Burssens, A.; Vermaut, G.; and |and |Van Ruymbeke, J.: Long-term study of the perioperative infection rate in 1007 total hip replacements using prophylactic cefamandole and other precautions. Arch. Orthop. and Trauma Surg., 106: 135-139, 1987.
18. Neu, H. C.: Cephalosporin antibiotics as applied in surgery of bones and joints. Clin. Orthop., 190: 50-64, 1984.
19. Ritter, M. A.; Stringer, E. A.; Williams, J.; and |and |Carlson, S.: The effect of hypotensive anesthesia on cephalosporin concentrations in serum, soft tissue, and bone. Clin. Orthop., 175: 218-222, 1983.
20. Schentag, J. J.; Jusko, W. J.; Vance, J. W.; Cumbo, T. J.; Abrutyn, E.; DeLattre, M.; and |and |Gerbracht, L. M.: Gentamicin disposition and tissue accumulation on multiple dosing. J. Pharmacokinet. and Biopharmaceut., 5: 559-577, 1977.
21. Schurman, D. J.; Hirshman, H. P.; Kajiyama, G.; Moser, K.; and |and |Burton, D. S.: Cefazolin concentrations in bone and synovial fluid. J. Bone and Joint Surg., 60-A: 359-362, April 1978.[Abstract/Free Full Text]
22. Schutzer, S. F., and |and |Harris, W. H.: Deep-wound infection after total hip replacement under contemporary aseptic conditions. J. Bone and Joint Surg., 70-A: 724-727, June 1988.[Abstract/Free Full Text]
23. Shanks, C. A.; Avram, M. J.; Ronai, A. K.; and |and |Bowsher, D. J.: The pharmacokinetics of d-tubocurarine with surgery involving salvaged autologous blood. Anesthesiology, 62: 161-165, 1985.[Medline]
24. Sue, D.; Salazar, T. A.; Turley, K.; and |and |Guglielmo, B. J.: Effect of surgical blood loss and volume replacement on antibiotic pharmacokinetics. Ann. Thoracic Surg., 47: 857-859, 1989.[Abstract]
25. Wiggins, C. E.; Nelson, C. L.; Clarke, R.; and |and |Thompson, C. H.: Concentration of antibiotics in normal bone after intravenous injection. J. Bone and Joint Surg., 60-A: 93-96, Jan. 1978.[Abstract/Free Full Text]
26. Williams, D. N.; Gustilo, R. B.; Beverly, R.; and |and |Kind, A. C.: Bone and serum concentrations of five cephalosporin drugs. Relevance to prophylaxis and treatment in orthopaedic surgery. Clin. Orthop., 179: 253-265, 1983.

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