Plasma Sodium: a Predictor of Perforation in Acute Appendicitis. (The NAP-study)

Children, Only Clinical Trial

Official title:

Plasma Sodium: a Predictor of Perforation in Acute Appendicitis. (The NAP-study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04806789
• Other study ID #: K 2021-2319
• Status: Recruiting
• Start date: June 1, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: March 2023
• Source: Karolinska Institutet
• Contact: Urban Fläring, Ass Prof
• Phone: +46708763900
• Email: urban.flaring[@]ki.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This clinical prospective diagnostic accuracy study assesses plasma sodium concentration using blood gas analysis at the emergency department in children, age 1-15 years, with suspected acute appendicitis. The overall assumption is that using plasma sodium as a biomarker, a cut-off value of <136 mmol/L will differentiate perforated from non-perforated acute appendicitis. In addition, traditionally used clinical diagnostic variables as well as radiology used in the diagnosis of acute appendicitis will also be obtained. Histopathology will be used to define if the appendix is perforated or not.

Description:

Background: The historical dogma that acute appendicitis always progresses to gangrene and perforation has been rejected. In addition, there is evolving evidence that medical treatment of non-perforated acute appendicitis is safe. On the other hand, perforated acute appendicitis requires appendectomy [Andersson]. Therefore, it is important to differentiate perforation from non-perforation in order to enable proper treatment.

In a pilot-study in children with acute appendicitis (n=80), plasma sodium was shown to be an independent predictor differentiating between perforated and non-perforated acute appendicitis [Lindestam]. Using plasma sodium at a cut-off value of <136 mmol/L, the odds ratio of having a perforated acute appendicitis was 31.9 (95% CI, 6.3- 161.9) with an area under the receiver operating curve of 0.93. Sensitivity and specificity were 0.87 (95 % CI 0.60-0.98) and 0.83 (95 % CI 0.72-0.91). Similar results have later been shown by another research group [Pogorelic]. Possible mechanism for lower plasma sodium among patients with perforation is higher concentration of arginin-vasopressin, which has previously been shown [Lindestam].

Methods: Participants (n=450 in total) whereof 150 in Sweden, 150 in Republic of South Africa, 50 in Germany, 50 in Denmark and 50 in Norway will be included in the study. The patients/parents will be asked for participation in the study and included after decision of surgery has been made by the attendant surgeon. At this timepoint, (i) variables from clinical examination/history (presence of right iliac fossa pain, rebound tenderness, duration of symptoms, vomiting, temperature, gender, age, weight, (ii) blood sampling: blood gas (including plasma sodium), C-reactive protein, neutrophiles, White blood cell count (obtained at the emergency department) and (iii) radiology has been obtained. No intervention is planned. These variables will also be used to calculate the Appendicitis Inflammatory Responce (AIR) score [Scott]. Thereafter, plasma sodium concentration will be added and the score will be recalculated.

After surgery, histopathology will be used to determine if the appendix is perforated or not.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: September 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 15 Years

Eligibility

Inclusion Criteria:

• Children with suspected acute appendicitis

Exclusion Criteria:

• Chronic metabolic disease

• Endocrinological disease

Related Conditions & MeSH terms

• Acute Appendicitis
• Acute Disease
• Appendicitis
• Children, Only

Locations

Country	Name	City	State
Sweden	Pediatric Perioperative Medicine and Intensive Care	Stockholm

Sponsors (5)

Lead Sponsor	Collaborator
Urban Fläring	Charite University, Berlin, Germany, Odense University Hospital, Oslo University Hospital, Red Cross War Memorial Childrens Hospital

Country where clinical trial is conducted

Sweden, 

References & Publications (4)

Andersson RE, Petzold MG. Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis. Ann Surg. 2007 Nov;246(5):741-8. doi: 10.1097/SLA.0b013e31811f3f9f. — View Citation

Lindestam U, Almstrom M, Jacks J, Malmquist P, Lonnqvist PA, Jensen BL, Carlstrom M, Krmar RT, Svensson JF, Norberg A, Flaring U. Low Plasma Sodium Concentration Predicts Perforated Acute Appendicitis in Children: A Prospective Diagnostic Accuracy Study. Eur J Pediatr Surg. 2020 Aug;30(4):350-356. doi: 10.1055/s-0039-1687870. Epub 2019 Apr 25. — View Citation

Pogorelic Z, Luksic B, Nincevic S, Luksic B, Polasek O. Hyponatremia as a predictor of perforated acute appendicitis in pediatric population: A prospective study. J Pediatr Surg. 2021 Oct;56(10):1816-1821. doi: 10.1016/j.jpedsurg.2020.09.066. Epub 2020 Oct 8. — View Citation

Scott AJ, Mason SE, Arunakirinathan M, Reissis Y, Kinross JM, Smith JJ. Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis. Br J Surg. 2015 Apr;102(5):563-72. doi: 10.1002/bjs.9773. Epub 2015 Mar 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma sodium concentration as a predictor for perforated acute appendicitis.	Plasma sodium will be dichotomized at 136 mmol/L. Lower concentration are hypothesized to indicate perforated acute appendicitis.	Possible predictive variables will only be obtained at one occation on the day of admission to the emergency department.
Secondary	Plasma sodium concentration adding precision to the diagnostic performance of "the Appendicitis Inflammatory Response (AIR) score".	This score uses anthropometric and laboratory values that will be obtained on admission to the emergency department. Adding plasma sodium to these values in regression analysis to increase possibility to predict perforated acute appendicitis.	Diagnostic values of interest are only obtained at one occasion on admission to the emergency department

External Links

•   Andersson
•   Lindestam
•   Pogorelic
•   Scott