Serum PCT levels increase postoperatively after uncomplicated cardiac surgery, reaching a peak level within 24 hours postoperatively 2930313233343536373839404142434445464748, and return to normal values in the following days (Figure 1). Peak PCT values, measured by the immunoluminometric assay, range from 0.5 to 7.0 ng/ml 2931323334353637383940424344464748.

Several factors may influence the evolution of serum PCT levels after cardiac surgery in the absence of postoperative complications. The specific surgical techniques used during the procedure may be one important factor. Franke et al. 34 reported higher PCT levels in patients after on-pump coronary artery bypass grafting (CABG) than in those after off-pump coronary artery bypass (OPCAB) surgery. Kilger et al. 29 found higher postoperative PCT levels in patients after OPCAB than in those after minimally invasive direct coronary artery bypass (MIDCAB), with median PCT levels of 2.0 ng/ml in the OPCAB and 0.7 ng/ml in the MIDCAB group. PCT levels were also higher after valvular surgery and thoracic aortic surgery than after CABG, with Loebe et al. 40 reporting PCT levels of greater than or equal to 5 ng/ml in 13% of patients who underwent CABG compared with 39% and 35% of those who underwent valvular and aortic surgery, respectively. A more pronounced increase in serum PCT levels was also reported after procedures involving ventriculotomy than after those involving atriotomy 4849. In paediatric patients, PCT levels increased more markedly after surgical repair of Tetralogy of Fallot than in those undergoing repair of ventricular septal defect or atrial septal defect 50. Intraoperative factors have also been shown to influence the postoperative evolution of serum PCT levels (for example, aortic cross-clamping time 30464849, duration of CPB 304546, and the duration of surgery 45).

Elevated PCT levels after surgical procedures may be explained by normal PCT kinetics. Three to four hours after injection of endotoxin in healthy subjects, PCT levels start to rise, reaching a maximum 24 hours thereafter 3. The return in PCT levels to normal within a few days after surgery after an uncomplicated postoperative course can be explained by the half-life of PCT (18 to 24 hours) 1 in the absence of a further insult that may induce more PCT production. Meisner et al. 51 showed that PCT production could be induced by various stimuli such as trauma, tissue injury, and others and that this non-specific and non-infectious stimulation of PCT is much lower than specific induction and much lower compared with other markers of the inflammatory response. The source of PCT production in these conditions could be explained by non-specific cytokine liberation from the injured tissue 52. Endotoxin release has also been reported after procedures involving the heart-lung machine 53.

The evolution of other clinically used markers of tissue inflammation/infection in relation to that of PCT was also reported in some comparative studies. C-reactive protein (CRP) levels increase postoperatively, peaking between postoperative days one and three and remaining elevated up to the second week postoperatively 29303554. irrespective of the extent of surgery 3334363842454654. Levels of interleukin-6 (IL-6), another marker of immune system activation, also increase postoperatively 34414648505556., peaking at 6 to 24 hours after surgery 344648, and are probably not related to the extent of surgery 48.

In summary, uncomplicated cardiac surgery induces a postoperative increase in serum PCT levels. Peak PCT levels are reached within 24 hours postoperatively and return to normal levels within the first week. This increase seems to be dependent on the surgical procedure, with more invasive procedures associated with higher PCT levels, and on intraoperative events, including aortic cross-clamping time, duration of CPB, and the duration of surgery.

Because of the marked overlap of signs and symptoms, diagnosis of infection still represents a major challenge in ICU patients after cardiac surgery. Early differentiation between SIRS after cardiac surgery and the development of perioperative infection is crucial to enable appropriate antibiotic therapy to be started and to prevent subsequent complications.

Several studies reported higher PCT levels after cardiac surgery in infected compared with non-infected patients 333536373841455758. Importantly, PCT levels remained elevated in the first week postoperatively 353738. The elevations in PCT levels were also reported to be more pronounced in bacterial and fungal infections than in viral infections of SIRS 3759. PCT levels ranged from a mean value of 4 ng/ml up to 30 ng/ml in infected patients, depending on the time at which infection was diagnosed. Initiating appropriate antibiotic therapy seems to bring about a marked reduction in PCT levels. Rothenburger et al. 35 reported a decrease in PCT levels in patients with systemic infection after cardiac surgery within 5 days after starting appropriate antibiotic therapy (from a median of 11 to 0.56 ng/ml).

In addition to PCT, CRP levels increase consistently after infection 353840 and both seem to be correlated to infection in this subgroup of patients 38. In contrast to PCT and CRP, white blood cell (WBC) count has no discriminative power in differentiating infected from non-infected patients after cardiac surgery 333854.

Rothenburger et al. 35 evaluated the diagnostic value of PCT and CRP in a group of 59 patients undergoing CPB. At a cutoff level of 4 ng/ml, PCT had a sensitivity of 86% and a specificity of 98% in predicting infection, whereas CRP at a cutoff level of 180 mg/l had a sensitivity of 100% and a specificity of 75%. Likewise, Aouifi et al. 39 reported that PCT was superior to CRP in predicting an infectious aetiology in 131 adult patients undergoing CPB. At a 1 ng/ml cutoff point, PCT had a sensitivity of 85% and a specificity of 95% in predicting infection, whereas CRP had a sensitivity of only 64% and a specificity of 84% at a cutoff level of 150 mg/l. Moreover, the area under the receiver operating characteristic (ROC) curves for prediction of infection was 0.82 and 0.62 for PCT and CRP, respectively (Figure 2). In addition, in 80 high-risk patients with an APACHE (acute physiology and chronic health evaluation) II score of greater than 20 undergoing CABG, Dörge et al. 57 found that PCT levels greater than 5 ng/ml had a sensitivity of 82% for discrimination of an infectious process but a poor specificity (only 45%). Meisner et al. 45 investigated the diagnostic value of PCT in predicting microbiologically proven infection in patients undergoing elective cardiovascular surgery. PCT levels greater than 2 ng/ml had a sensitivity of 83% and a specificity of 75% in this respect.

In summary, PCT values reported in infected patients are generally higher than in non-infected patients after cardiac surgery. PCT is superior to CRP in discriminating infections in this setting. PCT levels decrease markedly after initiation of appropriate antibiotic therapy. The dynamics of PCT levels, rather than the absolute values, could be important in identifying patients with infectious complications after cardiac surgery.

Several studies have suggested the presence of a correlation between serum PCT levels, the severity of sepsis syndromes, and the occurrence of organ dysfunction/failure after cardiac surgery 3637414459. Aouifi et al. 36 reported that PCT levels were correlated with the severity of sepsis. PCT levels reached up to 20 ng/ml in patients with sepsis and were as high as 97 ng/ml in patients who developed septic shock after CBP. Sablotzki et al. 4155 reported an elevation in PCT levels of more than 20 ng/ml during the first 3 days in patients suffering from multiorgan dysfunction syndrome (MODS) compared with patients with SIRS. Boeken et al. 59 reported mean PCT levels of 19 ng/ml in patients with sepsis, whereas sepsis-free patients had a mean PCT value of only 0.8 ng/ml. Recently, Celebi et al. 30 reported that PCT levels greater than 0.7 ng/ml, using the Kryptor assay, could predict postoperative organ failure in children undergoing cardiac surgery with a sensitivity of 85% and a specificity of 58%; at a cutoff level of 7.7 ng/ml, sensitivity and specificity rose to 100%. Brunkhorst et al. 9 found that PCT levels greater than 2 ng/ml discriminated patients with severe sepsis but not those with septic shock.

From the available literature, it is difficult to recommend cutoff points for discriminating patients according to the presence of organ dysfunction/failure or the severity of sepsis syndromes after cardiac surgery. In a group of 101 critically ill patients, Giamarellos-Bourboulis et al. 6061 failed to demonstrate any agreement between standard definitions of sepsis syndromes and those incorporating PCT levels as part of the diagnostic criteria.

Comparative data with other markers of tissue inflammation are scanty. Only two studies reported higher IL-6 levels, equivalent to the increase in PCT, in patients developing MODS on the first postoperative day compared with patients with SIRS without evidence of organ failure 4155, and WBC count 44 was poorly discriminative in this respect 4155.

In summary, PCT levels are higher with increased severity of sepsis syndromes and the presence of organ dysfunction/failure. Interpretation of PCT levels in this context should take these factors into consideration. PCT levels are correlated to the severity of sepsis syndromes; however, it is difficult to recommend cutoff points from the current literature.

The association between serum PCT levels and the severity of sepsis syndromes and organ dysfunction/failure has created interest in the possible prognostic value of PCT levels. PCT levels have been shown to be correlated to several severity-of-illness scoring systems used in clinical practice, including APACHE II 45 and SAPS (simplified acute physiology score) II 3945 scores. In addition, PCT levels correlated well with the degree of organ dysfunction/failure as assessed by the SOFA (sequential organ failure assessment) score 45. Meisner et al. 45 showed that PCT levels correlated well to the maximum values of SOFA score over the first 2 postoperative days in 208 patients undergoing CPB. Indeed, several studies 4041555762 have reported higher PCT levels in non-survivors after cardiac surgery compared with survivors. However, the discriminative power of PCT in this respect has been less investigated 41555762. Dörge et al. 57 found that PCT levels greater than 10 ng/ml 24 hours postoperatively could discriminate non-survivors in a high-risk group of patients after CPB with a sensitivity of 72% but with a low specificity (51.3%). However, Fritz et al. 62 reported that a PCT level as low as 2.8 ng/ml was the best cutoff for predicting 28-day mortality in patients after CABG. Similarly, Celebi et al. 30 reported predictive values of postoperative PCT for mortality in children undergoing cardiac surgery. At a cutoff level of 34.2 ng/ml, PCT had a sensitivity of 100% and a specificity of 90%, whereas at a cutoff level of 5 ng/ml, PCT had a sensitivity of 100% and a specificity of 65% in predicting mortality.

PCT levels were also found to be related to the development of postoperative complications 4245465763. Lecharny et al. 42 described higher mean PCT levels in patients who developed postoperative myocardial infarction than in those with an uneventful postoperative course. Meisner et al. 45 demonstrated a correlation between postoperative PCT levels in terms of the development of SIRS, respiratory failure, and the need for positive inotropic support. Likewise, Dörge et al. 57 reported higher PCT levels in patients who developed postoperative organ failure than in those with an uncomplicated postoperative course. Adamik et al. 63 reported that after CPB, PCT levels remained unchanged in patients with an uneventful recovery and increased in patients with complications, especially in those who developed renal and hepatic dysfunction in addition to respiratory and circulatory insufficiency. Using a cutoff value of just 2.0 ng/ml, the positive and negative predictive values for postoperative complications were 100%/93% and 100%/87% on the first and second postoperative days, respectively. CRP does not seem to be useful as a prognostic marker 36, likely due to its prolonged elevation after an uneventful postoperative course.

In summary, PCT levels are consistently higher in patients with a poor outcome and in those who develop postoperative complications. Further studies are needed to define cutoff points and to incorporate PCT levels in useful prediction models.

Another potentially useful implication of serum PCT measurement is the differential diagnosis of postoperative complications in critically ill patients who have undergone heart transplantation. Differentiation between postoperative infection and rejection is important in order to be able to initiate appropriate therapy. Several studies 3758646566 have evaluated the role of PCT in patients after heart and/or lung transplantation. In 12 patients undergoing endomyocardial biopsy after heart transplantation, Boeken et al. 37 described elevated PCT levels in patients with proven bacterial or fungal infection, whereas patients who developed graft rejection had almost normal PCT levels. Patients suffering from viral infections had PCT levels comparable with those with graft rejection. Hammer et al. 58 reported similar findings in a cohort of 78 patients after heart, lung, or heart and lung transplantation. CRP levels were equally elevated in all groups. Hammer et al. 64 also reported higher PCT levels in patients with systemic infections than in those with local infection after heart and lung transplantation. PCT levels were almost within normal limits in patients with acute rejection; CRP levels, however, were similarly elevated in all groups 64.

In summary, PCT is useful in differentiating acute graft rejection after heart and/or lung transplantation from bacterial and fungal infections. PCT levels typically remain unchanged after acute rejection but increase markedly after bacterial and fungal infections. Systemic infections are associated with more PCT elevation than is local infection. Viral infections are difficult to identify based on PCT measurements, being only slightly elevated in these patients. CRP levels do not seem to be useful in this setting, because they remain equally elevated regardless of the type of postoperative complication.