Clinical trial NCT04213040: Procalcitonin and Postoperative Outcome After Open-heart Surgery
Official title: Is Procalcitonin a Valuable Marker for the Identification of Postoperative Complications After Open-heart Surgery With Cardiopulmonary Bypass?
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Open Heart Surgery
Cardiopulmonary Bypass
Procalcitonin
C-reactive Protein
Lactate
Outcome
Postoperative Complications
Keywords: Open heart surgery
Cardiopulmonary bypass
Procalcitonin
C-reactive protein
Lactate
Outcome
Postoperative Complications
Lead sponsor: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
Sponsor class: OTHER_GOV
First posted: 2019-12-30
Enrollment: 214
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study is performed on a patient population undergoing open-heart surgery with cardiopulmonary bypass.

Brief summary: The aim of this study was to investigate the impact of serum values of procalcitonin (PCT), C-reactive protein (CRP) and lactate to predict postoperative complications in the early postoperative period after open-heart surgery with cardiopulmonary bypass (CPB).

Detailed description: The cardiopulmonary bypass (CPB) causes an inflammatory response secondary to the activation of cytokine systems in the whole body. The causes of this inflammation have been discussed extensively in the literature. As a concise summary the causes can be listed as; 1- the surgical stress, 2- the recognition of bypass circuit as an artificial surface by the blood components, 3- ischemia-reperfusion injury, 4- endotoxemia. After open-heart surgery with CPB, the development of several postoperative complications including myocardial dysfunction, respiratory failure, renal and neurologic dysfunction, bleeding disorders, altered liver function, and, multiple organ failure has been demonstrated to be related to the inflammatory response. Procalcitonin (PCT), is a 116-amino-acid protein that is produced in the liver and peripheral mononuclear cells and the normal serum PCT value is below 0.1 ng/mL in patients without signs of systemic inflammation. Serum PCT levels increase postoperatively after open-heart surgery and a peak level of 0.5 to 7.0 ng/mL is reported at 24 hours after the operation and serum PCT values decrease to normal values within seven days.

Serum C-reactive protein (CRP) values are often abnormally elevated after open-heart surgery as a result of an inflammatory response and it has not been found to be a useful prognostic marker due to its prolonged elevation after cardiac surgeries. In the literature, there are studies showing that serum PCT levels are consistently higher in patients with postoperative complications, however, a cutoff point for serum PCT to determine the risk of possible poor outcome has not been well studied. A recent study demonstrated that after CPB, serum PCT increased in patients with poor outcome especially in those who developed renal and hepatic dysfunction in addition to respiratory and circulatory insufficiency. This study demonstrated a cut off value of 2 ng/mL to predict postoperative complications. In another study, a PCT level of 2.8 ng/mL was found to be a cut off value to predict 28-day mortality in patients after coronary artery bypass grafting (CABG) however, it has been pointed out that there is a need for further studies.

The aim of our study was to investigate a relation between serum values of CRP, PCT, and lactate and development of postoperative complications (circulatory failure, pneumonia, respiratory insufficiency, sepsis, reoperation, hemorrhage, tamponade, need of inotropic support, myocardial infarction, acute kidney injury), in patients undergoing open-heart surgery with CPB. A sample size of 72 patients would have a power (1-ß) of 80% to detect a difference in serum PCT level of 10% (1 standard deviation) difference between patients with postoperative complications (n=36) and without postoperative complications (n=36) using 2-sided significance and an α=0.05.

Eligibility criteria: Inclusion Criteria:

1. Older than 18 and younger than 80 years old,
2. Elective open heart surgery with cardiopulmonary bypass (CPB),
3. American Society of Anesthesiology (ASA) physical status of 2 or 3.

Exclusion Criteria:

1. Perioperative signs of infection (preoperatively, during operation or postoperatively during the study period) including a report of fever greater than 38 degrees centigrade, increase in white blood cell count, increase in C-reactive protein value,
2. The detection of pneumonia including infiltration in chest x-ray,
3. The diagnosis of multiple organ failure,
4. The use of corticosteroids or non-steroidal anti-inflammatory drugs within the last seven days before surgery.

Primary outcomes:
measure: The comparison of serum procalcitonin values postoperatively
timeFrame: Postoperatively every day starting on postoperative 12 hours, postoperative days 1 through 5.
measure: The comparison of serum-reactive protein values postoperatively
timeFrame: Postoperatively every day starting on postoperative 12 hours, postoperative days 1 through 5.
measure: The comparison of serum lactate values postoperatively
timeFrame: Postoperatively every day starting on postoperative 12 hours, postoperative days 1 through 5.
Secondary outcomes:
measure: Complications
timeFrame: Postoperatively for a duration of seven days after operation.
Other outcomes:
Locations:
Study officials:
affiliation: Pendik Bolge Hospital
name: Ayse Baysal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Warren OJ, Smith AJ, Alexiou C, Rogers PL, Jawad N, Vincent C, Darzi AW, Athanasiou T. The inflammatory response to cardiopulmonary bypass: part 1--mechanisms of pathogenesis. J Cardiothorac Vasc Anesth. 2009 Apr;23(2):223-31. doi: 10.1053/j.jvca.2008.08.007. Epub 2008 Oct 19. No abstract available.
citation: Vohra HA, Whistance R, Modi A, Ohri SK. The inflammatory response to miniaturised extracorporeal circulation: a review of the literature. Mediators Inflamm. 2009;2009:707042. doi: 10.1155/2009/707042. Epub 2010 Jan 13.
citation: Sponholz C, Sakr Y, Reinhart K, Brunkhorst F. Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature. Crit Care. 2006;10(5):R145. doi: 10.1186/cc5067.
citation: Aouifi A, Piriou V, Blanc P, Bouvier H, Bastien O, Chiari P, Rousson R, Evans R, Lehot JJ. Effect of cardiopulmonary bypass on serum procalcitonin and C-reactive protein concentrations. Br J Anaesth. 1999 Oct;83(4):602-7. doi: 10.1093/bja/83.4.602.
citation: Adamik B, Kubler-Kielb J, Golebiowska B, Gamian A, Kubler A. Effect of sepsis and cardiac surgery with cardiopulmonary bypass on plasma level of nitric oxide metabolites, neopterin, and procalcitonin: correlation with mortality and postoperative complications. Intensive Care Med. 2000 Sep;26(9):1259-67. doi: 10.1007/s001340000610.
citation: Fritz HG, Brandes H, Bredle DL, Bitterlich A, Vollandt R, Specht M, Franke UF, Wahlers T, Meier-Hellmann A. Post-operative hypoalbuminaemia and procalcitonin elevation for prediction of outcome in cardiopulmonary bypass surgery. Acta Anaesthesiol Scand. 2003 Nov;47(10):1276-83. doi: 10.1046/j.1399-6576.2003.00239.x.
citation: Sablotzki A, Dehne MG, Friedrich I, Grond S, Zickmann B, Muhling J, Silber RE, Czeslick EG. Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery. Eur J Med Res. 2003 Feb 21;8(2):71-6.
citation: Meisner M, Rauschmayer C, Schmidt J, Feyrer R, Cesnjevar R, Bredle D, Tschaikowsky K. Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications. Intensive Care Med. 2002 Aug;28(8):1094-102. doi: 10.1007/s00134-002-1392-5. Epub 2002 Jul 6.
citation: Klingele M, Bomberg H, Schuster S, Schafers HJ, Groesdonk HV. Prognostic value of procalcitonin in patients after elective cardiac surgery: a prospective cohort study. Ann Intensive Care. 2016 Dec;6(1):116. doi: 10.1186/s13613-016-0215-8. Epub 2016 Nov 23.