F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection

In this clinical study we demonstrated the feasibility and additional value of combined FDG-PET/CT scans in ventilated critically ill patients. The high sensitivity and specificity are promising, considering the fact that the patients represent a subgroup of critically ill patients in which the absence or presence of an infection could not be obtained with conventional diagnostic procedures. Naturally, identification of the site of infection is essential to institute the most appropriate therapy. The high specificity of 79% indicates that in this small, highly selected group of patients in whom no diagnosis could be reached with conventional diagnostics, FDG-PET/CT scanning appears to be of additional value in detecting focal infection and inflammation. Although one may argue that, e.g., sinusitis or pneumonia could be diagnosed by CT alone, CT scans of the sinuses frequently show air-fluid levels whose clinical relevance is unclear, and chest CT scans frequently show pulmonary abnormalities consistent with atelectasis, pleural effusion and infiltrates in ventilated ICU patients. In our opinion, the addition of PET scanning to detect increased metabolism consistent with inflammation in these lesions has additional value in deciding whether or not the found abnormalities on the CT scan are actually regions of infection and the cause of symptoms and signs of the patient.

The high negative predictive value is also of major clinical importance to exclude a clinically important infection and prevent patients from being treated with antibiotics or undergoing unnecessary invasive procedures. As a measure of the post-test probability compared to the estimated pre-test probability of an infection the positive and negative likelihood ratio was calculated, showing that the FDG-PET/CT scan is of evident additional clinical value to indicate and exclude patients with the disease.

Up to now, scintigraphic imaging has played a very limited role in detecting suspected focal infections in ICU patients, as only two ICU case series are available in the literature. In a retrospective study, Kao et al. [20] investigated the value of Tc-99m labeled leucocyte-scintigraphy in detecting a source for occult sepsis in 25 ICU patients, demonstrating a sensitivity of 96% and a specificity of 84%. However, sensitivity and specificity were not calculated per patient, but per body region, resulting in more true negative sites and thus a higher specificity. Minoja et al. [21] prospectively evaluated the use of Tc-99m-labeled leukocyte scintigraphy in detecting the cause of occult sepsis in a group of 26 surgical and trauma patients and found a sensitivity and specificity of 95 and 91%, respectively. It is important to note that scintigraphic scans using Ga-67, In-111-labeled or Tc-99m labeled leukocytes have disadvantages, such as the amount of blood needed to harvest enough leukocytes (up to 120 ml), handling of potentially infected blood products, high radiation burden, and the long time span between injection and diagnosis. Advantages of FDG-PET are higher resolution, sensitivity in chronic low-grade infections and high accuracy in the central skeleton [22]. Furthermore, the time between FDG-injection and diagnosis is approximately 1 h, so results are available much sooner than in case of other nuclear medicine techniques.

Our study is limited by several factors. First, in some cases there was a specific suspicion of a localized infection, possibly increasing the a priori chance of an infection. However, we chose to describe the daily standard practice in this observational study, thereby accepting the differences in indications of PET/CT scanning. Second, a final diagnosis could not be established in all patients. This is especially important in the group of patients with negative FDG-PET/CT scans, since missing a diagnosis of focal infection can have serious consequences. Nevertheless, in none of the 11 patients with a negative FDG-PET/CT scan was a subsequent infectious diagnosis reached. When additional diagnostic procedures showed normal results and follow-up did not reveal a diagnosis, in the absence of a real gold standard, it seemed reasonable to presume that a focal infection with therapeutic consequences was not the cause of the signs or symptoms of the patient. However, several patients with normal FDG-PET/CT scans did receive short courses of antibiotic treatment, so the presence of an infection cannot be ruled out completely. In addition, some of the patients with a normal FDG-PET/CT scan developed an infectious complication more than 2 weeks later during their ICU stay. It is difficult to exactly determine whether these infectious processes could have been present at the time of the FDG-PET/CT scan. However, because of the fact that all other diagnostic tests performed at the time of the FDG-PET/CT scans in these patients were also normal, we considered it unlikely that these infections were present at the time of the FDG-PET/CT scan, and we considered these FDG-PET/CT scans true negative when no focal infection was diagnosed in the 2 weeks following the scan. Despite these limitations, our results indicate that a normal FDG-PET/CT scan excludes an important infectious process needing drainage or prolonged antibiotic treatment. To our knowledge, this is the first study evaluating the additional value of FDG-PET/CT scanning in diagnosing focal infections in ventilated critically ill patients. In accordance, studies evaluating PET scanning in diagnosing FUO in non-critically ill patients showed comparable results [14‐16, 23‐25]. Our group previously and more specifically investigated the role of FDG-PET in a subgroup of 48 non-critically ill, hospitalized patients with a suspected focal infection or inflammatory disease and found that 38 out of 55 FDG-PET scans were abnormal, of which 36 correctly pointed to the cause of the symptoms. In addition, a negative predictive value of 100% was found [16]. These findings indicate that in both non-ICU as well as critically ill ICU patients a negative PET/CT scan appears to exclude a focal infection almost certainly as a cause of the clinical symptoms.

In conclusion, our experience demonstrates the feasibility and potential value of the FDG-PET/CT scan, and it appears to be a promising tool in detecting and excluding focal infection in critically ill patients. Since the exact role of FDG-PET/CT scanning in critically ill ICU patients is yet undefined, we have to be vigilant to potential hazardous additional diagnostic consequences of the results of this technique. Nevertheless, the patient that underwent a pericardiocenthesis that turned out to be negative was the only case of the study where an additional invasive procedure was performed with a clear detrimental risk/benefit ratio. In this specific case the decision to perform a pericardiocenthesis was not only based on the results of the FDG-PET/CT scan, but also on the results of echocardiography. In the other 13 patients with a positive FDG-PET/CT scan, subsequent diagnostic tests resulted in the final diagnosis.

We propose that the use of the FDG-PET/CT scan should be considered earlier in critically ill patients suspected of an infection. Whether FDG-PET/CT scanning can be of additional value in the early detection of specific types of focal infection notoriously difficult to diagnose (e.g., mediastinitis, metastatic abscesses) will be the subject of future research.