Sodium and water homeostasis in children admitted with acute appendicitis: a prospective study

Abstract

To the Editor In 2011 we began a randomized clinical trial (ISRCTN 43896775) to evaluate the safety and efficacy of near-isotonic compared with hypotonic fluid therapy in maintaining postoperative plasma sodium concentration (PNa) within the normal range. 1 During the screening period, post-surgery, most patients displayed hyponatremia. Since normal PNa levels were an inclusion criterion, the trial was prematurely terminated due to poor accrual. We hypothesized that they may have had high circulating plasma levels of the antidiuretic hormone arginine-vasopressin (AVP) and that the prescription of intravenous hypotonic fluid therapy may have been a contributing factor to their hyponatremia. Consequently, we revised our local recommendations for fluid therapy (vide infra). With this background, and considering that acute appendectomy is the most frequent pediatric operative procedure, the main aim of this prospective observational single-center cohort study in children was to evaluate the changes in PNa from hospital admission to the end of surgery in the actual clinical setting. Since the pathophysiology of sodium and water homeostasis in the preoperative period is relatively unexplored, we also investigated the renal handling of sodium, as well as key hormones involved in sodium and water homeostasis. This study was conducted in Sweden, from 31 May 2016 to 4 July 2017. Ethical approval was given by the Ethical Review Board in Stockholm (2016/181–31/2). This study protocol was registered at the Australian New Zealand Clinical Trial Registry (ANZCTR 12617000047392). All parents provided voluntary written informed consent for their children to participate in this study. During the study period, 221 previously healthy children were admitted for suspected appendicitis. Since the enrollment of potential eligible participants was limited to the shift when our dedicated study team was working, 118 patients were not asked to participate, 7 declined participation, and 9 had been enrolled in another study. Eighty-seven children accepted participation, with 7 of these not receiving surgery and 28 excluded due to incomplete laboratory data. Our study population consisted of 52 children (35 males). All the patients fasted from admission until surgery and had postoperative histologically verified appendicitis: phlegmonous in 29 cases, gangrenous in 14 cases and perforated in 9 cases. On admission, our patients displayed symptoms such as abdominal pain, fever, nausea and/or vomiting, and poor fluid intake. Since the degree of extracellular fluid deficit is difficult to assess only on clinical grounds, they were arbitrarily considered to have a mild dehydration, i.e., 5% loss of body weight. All patients received an intravenous infusion of 50mL/kg of Ringer’s acetate solution (131 mmol/L sodium, 4 mmol/L potassium, 2 mmol/L magnesium, 110mmol/L chloride, 30mmol/L acetate; Fresenius Kabi®) over four hours. In 33 patients, this infusion was followed by a maintenance fluid and electrolyte therapy phase consisting of a hypotonic 0.23% normal sodium chloride (40 mmol/L sodium, 20 mmol/L potassium, 60 mmol/L chloride; extempore solution) in 5% glucose solution until the start of the surgery. The fluid rate was decreased to 80% at the maintenance stage in order to minimize the undesirable effects of any unintended volume overload and fluid retention. The other 19 children did not receive the preoperative maintenance fluid and electrolyte therapy because they were operated on while receiving Ringer’s acetate infusion or shortly afterwards. Anesthesia was induced with fentanyl, propofol or thiopental, and rocuronium and maintained with sevoflurane. Fluids were administered at anesthetist’s discretion during surgery. On admission (baseline), and directly after surgery PNa, plasmapotassium (PK), plasma-chloride (PCl), plasma-albumin (PAlb), plasma-creatinine (Pcr), plasma-renin, plasma-aldosterone, plasma-AVP, serum-osmolality (SOsm), urine osmolality (UOsm), urine creatinine (Ucr), and urine sodium (UNa) were investigated. Plasma sodium was also analyzed at induction of anesthesia. Routine laboratory tests were performed according to accredited hospital clinical laboratory procedure. The plasma-renin concentration was determined from EDTA-plasma that was incubated with plasma from a nephrectomized sheep followed by radioimmunoassay of angiotensin I through the antibodytrapping method as described by Poulsen and Jørgensen. Concentrations were measured by the rate of angiotensin I formation and standardized in terms of international units per liter (IU/L) based on the World Health Organization International Standard (ref. no. 68–356; National Institute for Biological Standards and Control, Hertfordshire, UK), with samples of 0.05 IU/L included in every run of the plasma-renin assay. The interassay coefficient of variation was 6%. Plasma-aldosterone was determined by ELISA (MS E-5200, LDN, Labor Diagnostika Nord, Germany). Human EDTA-plasma pool was used as an internal inter-assay standard. The inter-assay coefficient of variation was 4.3%. Vasopressin levels were determined by radioimmunoassay as previously described, using a specific VP antibody (AB3096). Vasopressin was extracted from plasma using Sep-Pak Plus C18 extraction cartridges (Waters Corporation, Milford, MA). The detection limit was 0.10 pg/mL plasma and the inter-assay coefficient of variation was 8%. The fractional excretion of sodium (FENa) was calculated from a spot urine sample taken at baseline and at the end of surgery, as follows: