Clinical trial NCT04806789: Plasma Sodium: a Predictor of Perforation in Acute Appendicitis. (The NAP-study)
Official title: Plasma Sodium: a Predictor of Perforation in Acute Appendicitis. (The NAP-study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Appendicitis
Children, Only
Keywords: Acute appendicitis
Children
Plasma Sodium
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: Charite University, Berlin, Germany
name: Red Cross War Memorial Childrens Hospital
name: Oslo University Hospital
First posted: 2021-03-19
Enrollment: 451
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children with suspected acute appendicitis

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Children with suspected acute appendicitis

Exclusion Criteria:

* Chronic metabolic disease
* Endocrinological disease

Primary outcomes:
measure: Plasma sodium concentration as a predictor for perforated acute appendicitis.
timeFrame: Possible predictive variables will only be obtained at one occation on the day of admission to the emergency department.
Secondary outcomes:
measure: Plasma sodium concentration adding precision to the diagnostic performance of "the Appendicitis Inflammatory Response (AIR) score".
timeFrame: Diagnostic values of interest are only obtained at one occasion on admission to the emergency department
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Pediatric Perioperative Medicine and Intensive Care
Study officials:
affiliation: Karolinska Institutet
name: Urban Fläring, Ass Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.