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Ann Thorac Surg 1996;62:1412-1416
© 1996 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Diagnosing Sternal Wound Infections With ^99mTc-Labeled Monoclonal Granulocyte Antibody Scintigraphy

Departments of Thoracic Surgery, Infectious Diseases, Diagnostic Radiology, and Hospital Physics, Karolinska Hospital, Stockholm, Sweden

Accepted for publication June 14, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. Postoperative mediastinitis is a serious complication of thoracic operations. The diagnosis can sometimes be difficult, especially in cases with subacute clinical presentation. The aim of this study was to assess the clinical use of granulocyte scintigraphy and tomography in the diagnosis of postoperative wound infection and mediastinitis.

Methods. Twenty-nine patients after cardiothoracic operations were included, of whom 5 patients with a normal postoperative course formed the control group. We injected technetium 99m-monoclonal antigranulocyte antibodies and performed single-photon emission computed tomography after 4 and 20 hours.

Results. Twenty-three patients had both the early and the later scan; the remaining 6 had only the early scan. Seven scans indicated infection: 3 cases of mediastinitis, 2 cases of superficial wound infection, 1 case of infection in a synthetic aortic graft, and 1 case of osteitis. All were verified by bacterial culture. There was one false-negative scan; this patient had only the early registration and then was explored.

Conclusions. This method when combined with the tomographic scan option is able to distinguish between deep and superficial infections. Two registrations must be made for optimal results.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
See also page 1416 and page 1417.

Mediastinitis is a potentially life-threatening complication of open heart operations that requires prompt diagnosis for optimal treatment. Diagnosis may be difficult in the early postoperative period because of the general inflammatory reaction to operative trauma and extracorporeal circulation, which includes fever, leukocytosis, and elevated C-reactive protein [1]. Patients with obvious signs of sternal wound infection or sternal dehiscence are rapidly brought to operation, but those with an unclear clinical presentation present a diagnostic dilemma. Computed tomography is sometimes performed in these patients, but the nature of swelling, fluid, and gas depicted is nonspecific, and metallic implants may reduce the image quality [2]. Bone scintigraphy and scintigraphy using gallium 67-citrate are nonspecific, and the images obtained are generally affected by the high background activity [3].

Granulocyte scintigraphy has been shown to be effective in detecting purulent infections and gives a more specific diagnosis [4–7]. Several reports have described small series of such investigations in suspected sternal wound infection [2, 8–10]. However, only techniques of labeling the leukocytes in vitro have been used, and single-photon emission computed tomography (SPECT) has been used by only one group [2]. This study was performed to evaluate a commercially available technetium 99m–monoclonal antigranulocyte antibody in combination with SPECT examination for diagnosing postoperative sternal wound infection in a clinical setting.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
This investigation was designed as an open prospective study with a control group. Between 1993 and 1995, 29 patients were examined; 28 were operated on through a median sternotomy and 1 through a lateral thoracotomy, with ^99mTc-monoclonal antigranulocyte antibody and SPECT. Twenty-four patients with symptoms or signs suggesting postoperative infection of unclear nature and 5 control patients were included in the study. The age, sex, surgical procedure, indication for examination, and examination times are shown in Table 1. The scans were performed 5 to 166 days after operation in the symptomatic group and 6 to 7 days after operation in the control group. Four patients had scintigrams more than 1 month after operation.

The study was approved independently by two committees, the Ethics and the Isotope Committees of Karolinska Hospital, Stockholm, Sweden, on September 9, 1993. The patients received oral and written information before consenting to participate in the study.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The reconstructed three-dimensional images of isotope activity were used to produce the two-dimensional images seen in Figure 1. The normal activity distribution in a postoperative patient is illustrated in Figure 1, parts 1a and b. At the early registration (4 hours), there were high count rates giving images of good quality with low noise. Although the late examination (20 to 24 hours) is characterized by high noise because of a 16-fold reduction of activity after the physical decay of ^99mTc, the use of a highly efficient three-headed SPECT system allowed us to produce images with acceptable noise levels long after administration of the isotope. The granulocyte density is reflected by strong bone marrow activity, which was stable from the first examination to the second. The faint liver activity and strong splenic accumulation reflect the normal distribution of granulocytes. At the early examination, there was a faint circulating activity in the blood found in the heart and large vessels. The typical bifid sternum after median sternotomy is seen. Our 5 control patients were assumed to have normal scans. These scans formed the reference to which the other 24 scans were compared. Pathologic results were defined as clearly increased focal activity outside the activity distribution of the control patients or overwhelmingly increased and unevenly distributed bone marrow activity not explicable by the operation performed.

View larger version (111K): [in this window] [in a new window]   Fig 1. . Two-dimensional views of 99mTc-labeled granulocyte scintigraphy and single-photon emission computed tomography reconstructed from three-dimensional data. Parts 1a and b show normal images 4 and 24 hours after injection of the 99mTc-labeled antibody. Parts 2a and b (patient 7) show images of a patient with superficial sternal wound infection. The arrow indicates the infected area, which appeared normal in the earlier examination. Parts 3a and b (patient 3) show images of a patient with mediastinitis. An area around the sternum increases in activity from the first image to the second. Activity also can be seen behind the sternum on the transverse image. Part 4 (patient 2) shows the only examination of a patient with mediastinitis. The frontal view appears normal; the transverse view reveals a retrosternal process. (F = frontal view; L = lateral view; T = transverse view.)

Of the seven positive scans, 3 patients had only an early examination, 3 patients showed increasing activity of the infectious site from the first to the second examination, and 1 patient showed pathologic activity in the infected area only at the late examination. Of the 17 negative scans in the symptomatic group, 9 patients were diagnosed with some form of infection (see Table 1), including 1 patient with mediastinitis. Only one examination was made because the patient's condition deteriorated and he was taken to the operating room for urgent reexploration. The diagnosis was verified by culture. In the remaining 8 patients, no infection was found and all recovered. There were no hospital deaths from mediastinitis. We encountered no false-positive scans.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Various methods of granulocyte labeling have been used over the years [4]. The first clinically applicable method was based on separation and in vitro labeling of granulocytes from peripheral blood with indium 111 [11]. Later, a similar procedure using ^99mTc was developed [12]. This made the technique more widely available, improved image quality, and reduced the radiation dose. However, the cumbersome extracorporeal labeling procedure requiring aseptic handling, which restricted its use. The introduction of the monoclonal antibody for in vivo labeling of granulocytes solved these problems and made the examination readily available [13]. Consequently, this is today the optimal technique for granulocyte scintigraphy, although its applicability in the diagnosis of sternal wound infections has not yet been fully evaluated.

The bone marrow activity of the thoracic cage is of value as an anatomic reference, but it conceals possible intrathoracic activity to such an extent that SPECT is preferable. Figure 1, part 4 illustrates that the frontal projection does not always reveal retrosternal processes, possibly accounting for the limited success of granulocyte scintigraphy previously. The low sensitivity for superficial wound infections reported by Cooper and associates [9] is in contrast to our findings, and may be explained by the use of only planar registrations. The tomographic mode of examination provides sectional images, making it possible to localize an increased uptake also in the third dimension and thus to differentiate between increased uptake behind and in front of the sternal bone, which is much more doubtful in planar registrations. The tomographic registration also increases the contrast resolution, thereby increasing the sensitivity of the technique. It can be concluded that SPECT examination is essential for optimal visualization in granulocyte scintigraphy. This procedure involves transportation of the patient to the nuclear medicine department and investigation on a narrow examination table with the arms above the head during approximately 30 minutes. This procedure has not hindered us from carrying out the examination in any of our patients. In fact, we have found the method easy to perform even in our sicker patients. The antibody can be injected in the ward and the patient moved only for the scans.

Using the technique presented here with computer-aided digital image analysis, it is also possible to obtain a late registration (20 to 24 hours after injection of the antibody) despite the rather short half-life of ^99mTc. In the four positive scans for which two registrations were made, there was a relative increase in activity at the infectious site from the first to the second registration, despite the tendency of the image to deteriorate with time. This observation, coupled with the substantially reduced background activity, seems to emphasize the importance of the second registration. However, the patient's condition must be the deciding factor in determining whether to perform this second registration or to initiate therapy immediately. In 1 of our patients with mediastinitis, the first registration 3 hours after injection of the labeled antibody appeared normal. It is possible that the second registration would have revealed the infection. A negative SPECT examination with only the early registration should be regarded as incomplete, with a risk of a false-negative result.

The patients selected for this investigation showed signs of low-grade, nonfulminant infections of unclear origin. The overall diagnostic power of the ^99mTc-labeled monoclonal antigranulocyte antibody and SPECT examination in identifying postoperative sternal wound infections in this selected population was excellent. Furthermore, this method was able to distinguish between superficial and deep infection, but failed to diagnose bronchopneumonia. All 3 of our patients with bronchopneumonia had received intravenous antibiotics for several days before the scans. This may account for a diminished granulocyte concentration in the lung and failure to identify the focus of infection. Others have encountered the same phenomenon, and this warrants further investigation [3].

The use of monoclonal antibodies as opposed to labeling the granulocytes in vitro is an important methodologic improvement, but the examination still takes 24 hours. Thus, it is of use in selected cases but is not applicable to patients in a septic condition. We have found this method useful in diagnosing postoperative mediastinitis to minimize the delay in appropriate treatment. A positive scan suggested the need for exploration. A negative scan called for continued vigilance and close clinical observation, and the possible need to direct diagnostic efforts to extrathoracic foci.

Recent data suggest that using the small Fab` fragment of the antibody may allow earlier detection of infection [14]. If this fragment is used together with a high-quality mobile gamma camera suitable for ectotomographic examinations, most of the practical limitations of this method may be overcome.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Dr Bitkover, Department of Thoracic Surgery, Karolinska Hospital, S-171 76 Stockholm, Sweden.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

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