Procalcitonin and Postoperative Outcome After Open-heart Surgery

Is Procalcitonin a Valuable Marker for the Identification of Postoperative Complications After Open-heart Surgery With Cardiopulmonary Bypass?

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).

Study Overview

• Status: Completed
• Conditions: Postoperative Complications; Cardiopulmonary Bypass; Procalcitonin; Outcome; Lactate; C-reactive Protein; Open Heart Surgery
• Intervention / Treatment: Diagnostic test: Serum levels of Procalcitonin, C-reactive protein, lactate

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.

• Study Type: Observational
• Enrollment (Actual): 214

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study is performed on a patient population undergoing open-heart surgery with cardiopulmonary bypass.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Open-Heart Surgery for a six months duration; In a single group of patients including 146 patients undergoing openheart surgery during a period of six months, the collected parameters include; serum levels of procalcitonin, C-reactive protein, and lactate as well as postoperative complications and after this, depending on the development of postoperative complications or not in the intensive care unit patients were divided into two groups. The Group Without Complications, n=112, includes patients without a postoperative complication after open-heart surgery with cardiopulmonary bypass. The Group With Complications, n=34, includes patients with a postoperative complication after open-heart surgery with cardiopulmonary bypass.

Diagnostic test: Serum levels of Procalcitonin, C-reactive protein, lactate; Serum PCT, CRP, and lactate values were collected postoperatively every day starting on postoperative 12 hours, postoperative days 1 through 5. After the operation, all postoperative complications were recorded during the first seven days period. The relations between diagnostic tests and postoperative complications are sought by the use of the statistical analysis methods.; Other Names: Postoperative complications; Type of open-heart surgical operation (coronary artery bypass graft operation, mitral valve, aortic valve or multiple valvular surgeries)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The comparison of serum procalcitonin values postoperatively	Serum Procalcitonin values were collected postoperatively for five days and a change from the postoperative 12 hours value was evaluated using appropriate statistical analysis. Later, a repeated measures statistical analysis was also performed.	Postoperatively every day starting on postoperative 12 hours, postoperative days 1 through 5.
The comparison of serum-reactive protein values postoperatively	Serum C-reactive protein values were collected postoperatively for five days and a change from the postoperative 12 hours value was evaluated using appropriate statistical analysis. Later, a repeated measures statistical analysis was also performed.	Postoperatively every day starting on postoperative 12 hours, postoperative days 1 through 5.
The comparison of serum lactate values postoperatively	Serum Lactate values were collected postoperatively for five days and a change from the postoperative 12 hours value was evaluated using appropriate statistical analysis. Later, a repeated measures statistical analysis was also performed.	Postoperatively every day starting on postoperative 12 hours, postoperative days 1 through 5.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications	Postoperative complications were collected and recorded.	Postoperatively for a duration of seven days after operation.

Collaborators and Investigators

• Sponsor: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): July 31, 2013
• Study Completion (Actual): December 31, 2013

Study Registration Dates

• First Submitted: December 1, 2019
• First Submitted That Met QC Criteria: December 26, 2019
• First Posted (Actual): December 30, 2019

Study Record Updates

• Last Update Posted (Actual): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Procalcitonin; Outcome; C-reactive protein; Lactate; Cardiopulmonary bypass; Postoperative Complications; Open heart surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications
• Other Study ID Numbers: 2013.3/11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We can share the study protocol, clinical study report, the excel and spss data of our clinical work.
• IPD Sharing Time Frame: The data is available upon registration and it will be available in the web site if needed.
• IPD Sharing Access Criteria: Accessible to all researchers.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No