Elevated Procalcitonin in Patients After Cardiac Surgery: A Hint to Nonocclusive Mesenteric Ischemia Matthias Klingele, MD, Hagen Bomberg, MD, Aaron Poppleton, MBChB, Peter Minko, MD, Thimo Speer, MD, PhD, Hans-Joachim Sch€ afers, MD, and Heinrich V. Groesdonk, MD Department of Medicine, Division of Nephrology and Hypertension, and Departments of Anesthesiology, Intensive Care Medicine and Pain Medicine, Diagnostic and Interventional Radiology, and Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg/Saar, Germany

Background. Nonocclusive mesenteric ischemia (NOMI) can occur after cardiac surgery, commonly in conjunction with use of cardiopulmonary bypass. Some evidence suggests that serum procalcitonin (PCT) levels are increased in patients with mesenteric ischemia; however, an association between PCT and NOMI has not yet been studied. The current study investigates whether elevated serum PCT levels are found in patients exhibiting NOMI. Methods. In an observational cohort study of 865 patients undergoing elective cardiac surgery, 78 experienced NOMI. Preoperative and postoperative PCT levels were determined by means of enzyme-linked immunosorbent assay. Odds ratios and 95% confidence intervals were calculated by logistic regression analyses to predict accuracy of PCT in identifying patients with NOMI. Additional models were calculated, adjusting for potential confounders.

Results. Patients with NOMI had higher postoperative PCT levels than control patients (20.8 ± 3.2 ng/mL versus 2.3 ± 1.1 ng/mL; p < 0.001). Likelihood of experiencing NOMI increased with each nanogram per milliliter rise in postoperative PCT level (odds ratio, 2.61; 95% confidence interval, 2.05 to 3.32). Receiver operating characteristic analyses showed elevated serum PCT levels to accurately predict occurrence of NOMI (optimal cutoff value, 6.6 ng/ mL; area under the curve, 0.94; sensitivity, 71%; specificity, 94%). Conclusions. Postoperative measurement of PCT seems useful to improve the clinical and noninvasive identification of patients with NOMI after cardiac surgery.

N

onocclusive mesenteric ischemia (NOMI) is a notorious gastrointestinal complication after procedures involving cardiopulmonary bypass, with mortality rates of up to 90% [1, 2]. By impairing intestinal perfusion, NOMI causes extreme reduction or maldistribution of splanchnic blood flow [2, 3]. This intestinal ischemia compromises mucosal integrity with consequent bacterial translocation and bacteremia, with potential progression to multiorgan failure [2]. Although some perioperative risk factors such as the use of an intraaortic balloon pump, catecholamine support, or loss of sinus rhythm have been described [4], no specific factor for early detection of NOMI is currently available. Several clinical indicators for NOMI such as onset of oliguria or anuria, severe abdominal bloating and distention, borderline or elevated serum lactate, or metabolic acidosis act as warning signs [3, 4]. However, mesenteric angiography is recommended for reliable diagnosis and classification of

NOMI [3]. As such, a noninvasive method for early identification of patients at risk of having NOMI postoperatively could help reduce morbidity and mortality as a result of NOMI. Procalcitonin (PCT) is a 116-amino acid peptide secreted from thyroid parafollicular cells as the precursor of calcitonin [5]. Procalcitonin was shown to predict outcome in patients with acute mesenteric ischemia caused by arterial or venous embolism [6]. Moreover, PCT aids identification of patients with mesenteric ischemia after bowel obstruction [7]. Furthermore, postoperative elevated levels of PCT were described as being associated with complications after cardiac surgery [8, 9]. Nevertheless, the predictive value of PCT for NOMI after cardiac surgery remains unknown. For this reason we analyzed the predictive power of a single serum PCT measurement in identifying patients with NOMI after elective cardiac surgery.

Accepted for publication Oct 31, 2014.

Patients and Methods

Address correspondence to Dr Groesdonk, Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital of Saarland, Kirrbergerstrasse 1, 66421 Homburg, Germany; e-mail: [email protected].

A prospective cohort study was undertaken from January 1, 2010, to March 31, 2011. During this period 1,272 patients underwent cardiac surgery with extracorporeal

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KLINGELE ET AL POSTOPERATIVE ELEVATION OF PCT AND NOMI

circulation; of this total, 94 and 15 patients underwent urgent and emergency surgery, respectively. Of the 1,163 adult patients undergoing elective cardiac surgery, 298 refused participation in the study, resulting in a final study population of 865 individuals. Written informed consent was obtained from all patients. Ethical approval was obtained from the local ethics committee (Landes€ arztekammer des Saarlandes; ref. ID: 199/09).

Clinical Suspicion of Nonocclusive Mesenteric Ischemia Nonocclusive mesenteric ischemia was suspected clinically if at least two of four possible clinical indicators were given: new onset of oliguria or anuria; abdominal distention with decreased or absent bowel sounds; serum lactate level greater than 5.0 mmol/L or metabolic acidosis (base excess less than 5 mmol/L); or increase in vasopressor requirements by more than threefold from the end of surgery in the absence of hypovolemia.

Radiographic Analysis In patients with those changes being suggestive of mesenteric ischemia, angiography of the superior mesenteric artery was performed. All images were assessed by an experienced radiologist and an intensivist on a consensus basis. For diagnosis and assessment of severity we used our previously published scoring system [3]. This score is based on five criteria of image analysis: vessel morphology, contrast medium reflux into the aorta, contrast enhancement and distention of the intestine, and the time of portal vein filling. For each of these criteria the degree of radiographic changes attributable to NOMI resulted in a score of 0 to 2 or 3 points, as shown in Appendix Table 1. Addition of these scores results in a total score with a minimum of 0 (no changes caused by NOMI) and a maximum of 8 (considerable changes). A total score greater than 1 point was classified as NOMI. In this case, the angiographic catheter was left in the superior mesenteric artery for infusion of a prostacyclin analog (Ventavis [iloprost]; Actelion Pharmaceuticals US, Inc, South San Francisco, CA). The dose applied was chosen according to the severity of NOMI (2 to 6 ng , kg1 , min1). The dose was adjusted according to clinical development and terminated respectively.

Procalcitonin Measurement Blood sampling was performed directly before and the morning after surgery using 2.7-mL EDTA tubes (Sarstedt AG and Co, N€ umbrecht, Germany) and transported on ice. Samples were centrifuged (1,525g for 10 minutes at 4 C) with serum placed in polypropylene tubes (Sarstedt AG and Co) and stored at 80 C for further analysis. Procalcitonin concentrations were determined in the laboratory of the University Hospital Saarland by use of the Elecsys Brahms PCT automated electrochemiluminescence assay (Brahms AG, Henningsdorf, Germany) in the Cobas 8000 modular analyzer (Roche Diagnostics, Basel, Switzerland), per manufacturer’s instructions. The functional assay sensitivity (lowest quantifiable concentration with a between-run imprecision of

Elevated procalcitonin in patients after cardiac surgery: a hint to nonocclusive mesenteric ischemia.

Nonocclusive mesenteric ischemia (NOMI) can occur after cardiac surgery, commonly in conjunction with use of cardiopulmonary bypass. Some evidence sug...
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