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

Urban Fläring

Status: Completed

Conditions: Children, Only; Acute Appendicitis

Study type: Observational

Funder types: Other

Identifiers

NCT04806789

K 2021-2319

Details and patient eligibility

About

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.

Full 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.

Enrollment: 451 patients

Sex: All

Ages: 1 to 15 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children with suspected acute appendicitis

Exclusion criteria

• Chronic metabolic disease
• Endocrinological disease

Trial design

451 participants in 1 patient group

Children with suspected acute appendicitis

Description:

Cohort: Children with suspected acute appendicitis. Clinical examination (including history of nausea, vomiting, temperature, information of rebound tenderness, right iliac fossa pain, duration of symptoms, gender and weight) and blood samples will be obtained at the emergency department (blood gas, C-reactive protein, neutrophiles and white blood cell count). Radiology (ultrasound and/or computed tomography) will be performed thereafter. Outcome measures Primary outcome measure: Plasma sodium. To investigate if plasma sodium is an independent predictor of perforation in children with acute appendicitis. In advance, five variables (Plasma sodium, C-reactive protein, symptom duration, age and temperature) will be included in the final multivariable analysis