Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000047392
Ethics application status
Approved
Date submitted
1/12/2016
Date registered
10/01/2017
Date last updated
2/02/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Sodium concentration as a predictor for perforated appendicitis in children
Scientific title
Sodium concentration as a predictor for perforated appendicitis in children
Secondary ID [1] 290665 0
Nil known
Universal Trial Number (UTN)
Nil known
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Perioperative hyponatremia in pediatric surgical patients. 301195 0
Water balance disturbance in pediatric surgical patients 301196 0
Stress induced catabolism in pediatric surgical patients 301197 0
Appendicitis 301455 0
Condition category
Condition code
Surgery 300947 300947 0 0
Other surgery
Metabolic and Endocrine 300948 300948 0 0
Other endocrine disorders
Oral and Gastrointestinal 300951 300951 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
All patients with an expected appendicitis is asked for participation in the study. Also, parents are asked. The study period extends from inclusion to the end of the surgical procedure. Blood samples (3 ml) for the determination of blood gas (including sodium concentration), urea, osmolality, ketones, creatinine, cortisol, ADH, aldosterone and renin are taken at the emergency department by a specialist nurse (in addition to the routine samples) and at the end of surgery by a anaesthetic nurse. After induction of anesthesia a blood sample of blood gas and ketones (0,4 ml) is also taken. In addition, urine production is noted and samples are taken for the determination of osmolality, the concentrations of sodium, potassium, creatinine and urea. All the patients are fasted as part of the clinical routines. The volume of all given intravenous fluids during the study period are recorded. Hence the patients are given the normal clinical routines, the interventions are extra blood sampling and sampling from urine. The given fluid and the and the urine output are also recorded.
Intervention code [1] 296545 0
Not applicable
Comparator / control treatment
The primary aim is to investigate if serum sodium concentration is significantly lower in pediatric patients with perforated appendicitis as compared to pediatric patients not having perforation (gangrenous phlegmonous appendicitis). These two groups are compared. There are no conventional control group.
Control group
Active

Outcomes
Primary outcome [1] 300369 0
Serum sodium concentration compared between the two groups, perforated appendicitis vs non-perforated (gangrenous phlegmonous appendicitis).
Timepoint [1] 300369 0
At admission at the emergency department.
Primary outcome [2] 300595 0
Specificity and sensitivity of serum sodium at admission as a predictor of perforated vs non-perforated, established by review of surgical records.
Timepoint [2] 300595 0
At admission at the emergency department.
Secondary outcome [1] 329806 0
Rate of hyponatremia, defined as serum sodium concentration < 136 mmol/L.
Timepoint [1] 329806 0
From admission to the end of the surgical procedure.
Secondary outcome [2] 329807 0
Correlation between ADH and sodium concentrations, assessed by serum assay.
Timepoint [2] 329807 0
From admission to the emergency department to the end of the surgical procedure.
Secondary outcome [3] 329808 0
Correlation between serum ketone concentration and severity of appendicitis (by 5-point numerical rating scale designed for this study).
Timepoint [3] 329808 0
From admission to the emergency department to the end of the surgical procedure.
Secondary outcome [4] 330380 0
Correlation of occurance of hyponatraemia (defined as serum sodium concentration <136 mmol/L) with sodium administration (as recorded in the medical records).
Timepoint [4] 330380 0
From admission to the emergency department to end of the surgical procedure.
Secondary outcome [5] 330381 0
Correlation between aldosterone and sodium concentrations, assessed by serum assay.
Timepoint [5] 330381 0
From admission to the emergency department to end of the surgical procedure.
Secondary outcome [6] 330382 0
Correlation between renin and sodium concentrations, assessed by serum assay.
Timepoint [6] 330382 0
From admission to the emergency department to end of the surgical procedure.
Secondary outcome [7] 330383 0
Correlation of occurance of hyponatraemia (defined as serum sodium concentration <136 mmol/L) with free water administration (as recorded in the medical records).
Timepoint [7] 330383 0
From admission to the emergency department to end of the surgical procedure.
Secondary outcome [8] 330384 0
Correlation between serum ketone concentration and the amount of given glucose
Timepoint [8] 330384 0
From admission to the emergency department to end of the surgical procedure.

Eligibility
Key inclusion criteria
Previously healthy pediatric patients with suspected (ultrasound) appendicitis.
Minimum age
1 Years
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Hyponatremia < 136 mmol/L, significant chronic disease, severe hypovolemia requiring bolus fluid at the emergency department.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Normality will be assessed using the D’Agostino & Pearson omnibus normality test. Data normally distributed will be given as means and standard deviation (SD). Non-parametric data values are given as median and interquartile range (IQR). Student’s t-test, Wilson matched pair test, One-way ANOVA followed by Tukey’s post hoc test, were used when applicable using GraphPad Prism 5 (GraphPad Software, Inc.7825 Fay Avenue, Suite 230 La Jolla, CA 92037 USA).
Regarding the number of patients needed to be included to answer the primary question, it was not possible to calculate power when the study was designed due to lack of knowledge of the standard deviation in sodium concentration at admission in patients with and without perforated appendicitis. Our assumption of a SD of at least 4 was uncertain and would require 200 patients. Therefore, we analysed the difference and SD after 40 patients. The obtained information gave a SD of 2,5. Our assumption is still a significant difference of 2 mmol/L. From empirical data, approximately 15 % of the patients will have a perforated appendix and 85 % will not. The power calculation showed that including 80 patients (65 and 15 in each group) with an assumed difference of 2 mmol/L and an SD of 2.5 mol/L will give a power of 80 %.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
6/06/2016
Date of last participant enrolment
Anticipated
31/05/2017
Actual
4/07/2017
Date of last data collection
Anticipated
31/05/2017
Actual
4/07/2017
Sample size
Target
80
Accrual to date
Final
80
Recruitment outside Australia
Country [1] 8427 0
Sweden
State/province [1] 8427 0
Stockholm

Funding & Sponsors
Funding source category [1] 295094 0
Hospital
Name [1] 295094 0
Karolinska University Hospital
Country [1] 295094 0
Sweden
Primary sponsor type
Individual
Name
Urban Flaring
Address
Department of Pediatric Perioperative Medicine
Karolinska University Hospital
17176 Stockholm
Country
Sweden
Secondary sponsor category [1] 293914 0
Individual
Name [1] 293914 0
Per-Arne Lonnqvist
Address [1] 293914 0
Department of Pediatric Perioperative Medicine
Karolinska University Hospital
17176 Stockholm
Country [1] 293914 0
Sweden

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296445 0
Ethics committee of Stockholm
Ethics committee address [1] 296445 0
Regionala etikprovningsnamnden i Stockholm
Wiederstromska huset
Tomtebodavagen 18 A, plan 3.
17165 Solna
Ethics committee country [1] 296445 0
Sweden
Date submitted for ethics approval [1] 296445 0
12/05/2016
Approval date [1] 296445 0
23/05/2016
Ethics approval number [1] 296445 0
Dnr: 2016/181-31/2

Summary
Brief summary
There are mainly two purposes with this study. The primary aim is to elucidate if pediatric patients with perforated appendicitis have lower sodium concentration at admission to the emergency department and if low sodium concentration can serve as a predictor for the likelihood of a patient having appendix perforation. This is of clinical importance since appendicitis with a perforation needs to be diagnosed urgently, not delaying the surgical procedure so that complications can be avoided.

The main secondary question is to characterise sodium concentration from admission to the end of surgery in patients with appendicitis. Hyponatremia is often seen in acutely ill children, including surgical patients, and can be severe if maintenance fluids with a low sodium content is given. Severe hyponatremia can result in encephalopathy and even death. To a large extent this is caused by an increased production of the antidiuretic hormone arginine-vasopressin (AVP or ADH). However, when fluids for maintenance and/or rehydration that contain almost the same concentration of sodium as in normal serum are used, hyponatremia may occur. This may be explained by an expansion of the extra cellular volume resulting in a suppression of the hormones, renin and aldosterone. Also an increased secretion of atrial natriuretic or brain natriuretic factor can contribute to the development of hyponatremia in a hypervolemic state. The study will clarify the incidence of hyponatremia and to what extent the amount of sodium in the given fluid and the amount of fluid given contribute to hyponatremia and the incidence of syndrome of inappropriate antidiuresis (SIAD). This will be achieved by recording all fluid going into the patient and out of the patient by urine production. Also the hormones involved in the sodium turn-over (ADH, renin, aldosterone and cortisol) will be measured as well as osmolality in serum and urine. In urine also the concentration of creatinine, urea,
The results of this study may give sufficient information for the design of future interventional studies where the aim will be to elucidate optimal amount of sodium in the maintenance/rehydration fluid and the optimal amount of fluid.

Appendicitis in children common world wide and by studying these patients, it may be possible to generalise to other diagnosis requiring acute surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70890 0
Dr Urban Flaring
Address 70890 0
Department of Pediatric Perioperative Medicine
Karolinska University Hospital
17176 Stockholm
Country 70890 0
Sweden
Phone 70890 0
+46708763900
Fax 70890 0
Email 70890 0
[email protected]
Contact person for public queries
Name 70891 0
Dr Urban Flaring
Address 70891 0
Department of Pediatric Perioperative Medicine
Karolinska University Hospital
17176 Stockholm
Country 70891 0
Sweden
Phone 70891 0
+46 708763900
Fax 70891 0
Email 70891 0
[email protected]
Contact person for scientific queries
Name 70892 0
Dr Urban Flaring
Address 70892 0
Department of Pediatric Perioperative Medicine
Karolinska University Hospital
17176 Stockholm
Country 70892 0
Sweden
Phone 70892 0
+46708763900
Fax 70892 0
Email 70892 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLow Plasma Sodium Concentration Predicts Perforated Acute Appendicitis in Children: A Prospective Diagnostic Accuracy Study.2020https://dx.doi.org/10.1055/s-0039-1687870
N.B. These documents automatically identified may not have been verified by the study sponsor.