Strandby et al. BMC Anesthesiology (2017) 17:20 DOI 10.1186/s12871-017-0314-6 RESEARCH ARTICLE Open Access Plasma pro-atrial natriuretic peptide to estimate fluid balance during open and robot-assisted esophagectomy: a prospective observational study Rune Broni Strandby1*, Rikard Ambrus1, Niels H. Secher2, Jens Peter Goetze3, Michael Patrick Achiam1 and Lars Bo Svendsen1 Abstract Background: It remains debated how much fluid should be administered during surgery. The atrial natriuretic peptide precursor proANP is released by atrial distension and deviations in plasma proANP are reported associated with perioperative fluid balance. We hypothesized that plasma proANP would decrease when the central blood volume is compromised during the abdominal part of robot-assisted hybrid (RE) esophagectomy and that a positive fluid balance would be required to maintain plasma proANP. Methods: Patients undergoing RE (n = 25) or open (OE; n = 25) esophagectomy for gastroesophageal cancer were included consecutively in this prospective observational study. Plasma proANP was determined repetitively during esophagectomy to allow for distinction between the abdominal and thoracic part of the procedure. The RE group was 15° head up tilted during the abdominal procedure. Results: The blood loss was 250 (150–375) (RE) and 600 ml (390–855) (OE) (p = 0.01), but the two groups of patients were provided with a similar positive fluid balance: 1705 (1390–1983) vs. 1528 ml (1316–1834) (p = 0.4). However, plasma proANP decreased by 21% (p < 0.01) during the abdominal part of RE carried out during moderate head-up tilt, but only by 11% (p = 0.01) during OE where the patients were supine. Plasma proANP and fluid balance were correlated in the RE-group (r = 0.5 (0.073–0.840), p = 0.02) and tended to correlate in the OE group (r = 0.4 (−0.045–0.833), p = 0.08). Conclusion: The results support that plasma proANP decreases when the central blood volume is compromised and suggest that an about 2200 ml surplus administration of crystalloid is required to maintain plasma proANP during esophagectomy. Trial registration: Clinicaltrials.gov (NCT02077673). Registered retrospectively February 12th 2014. Keywords: Central blood volume, Abdominal surgery, Fluid balance, Plasma-atrial natriuretic peptide * Correspondence: [email protected] 1Department of Surgical Gastroenterology, University of Copenhagen, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen-Ø, Denmark Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Strandby et al. BMC Anesthesiology (2017) 17:20 Page 2 of 7 Background candidates for the study (Table 1). Data were collected Fluid administration affects outcome after surgery [1–3], by the investigators and remained confidential through- but it remains debated how much fluid should be ad- out the trial. Patients were excluded from the study if ministered and how the volume load is to be evaluated consent was withdrawn or disseminated disease was evi- [4, 5]. For colorectal surgery a “restricted” fluid regimen dent, i.e. only patients for whom the operation was com- seems profitable in regard to cardiopulmonary complica- pleted were included. tions and tissue healing [3, 6]. On the other hand, patients going through laparoscopic cholecystectomy appear to Anesthesia and interventions benefit from a “liberal” fluid regimen [1], probably because An i.v. line was established followed by a thoracic epi- the patients are head-up tilted. Deviations in postoperative dural catheter (Th7-Th9) and its position was evaluated outcome relate likely to how well the central blood vol- with the response to administration of 3 ml 2% lidocaine ume (CBV) is maintained during surgery. Consequently, with adrenaline (SAD, Amgros I/S, Denmark). Induction so-called individual goal-directed fluid therapy aims at of anesthesia was with propofol (2.0 mg/kg) and remi- maintaining a CBV that does not limit, e.g. stroke volume fentanil (0.5 μg/kg) followed by placement of a double- (SV) during surgery, eventually based on a report of SV by lumen endobronchial tube after neuromuscular blockade minimally invasive apparatus [5, 7]. by cisatracurium. Anesthesia was maintained by propo- We considered that plasma atrial natriuretic peptide fol (5–10 mg/kg/h) and remifentanil (1.75–2.25 mg/h) (ANP) would indicate whether filling of the heart is and ventilation was adjusted to an end-tidal CO2 tension of maintained during surgery. ANP – but not “brain” natri- 28–32 mmHg (Dräger CATO; M32040, Lübeck, Germany). uretic peptide [8] - reacts rapidly to a reduction in CBV, Guided by ultrasound a central venous catheter was estab- e.g. during head-up tilt [9] or sitting or standing up [8] lished via the right jugular vein for infusion of fluids and, if as with pressure breathing [10] demonstrating independ- considered necessary vasopressors (Table 2). LR (3 ml/kg/ ence of even a large increase in central venous pressure h) was supplemented by 5% Voluven® or human albumin [11]. Compared to plasma ANP, plasma pro-ANP 5% if considered in need by the anesthesiologist. Red blood (proANP) is stable with a half-life of 60–120 min [12] cells were administered when hemoglobin was lower than and during cystectomy, plasma proANP decreases with 4.5 or 5.5 mmol/l if the patient was known with cardio- the perioperative blood loss and, conversely increases pulmonary disease. For epidural anesthesia 4 ml bupiva- with a positive fluid balance when administration is caine (5 mg/ml, SAD) was administered before start of the based mainly on lactated Ringer’s solution (LR) [13]. procedure in both groups. Analgesia was maintained with We determined plasma proANP and perioperative bupivacaine (4 ml/h) with morphine (comb. 2.5 mg and 50 fluid balance during open (OE) and robot-assisted hybrid microgram/ml, SAD, Amgros I/S, Denmark) before start of (RE) esophagectomy. During esophagectomy CBV could be compromised not only by an eventual blood loss but also by, e.g. epidural analgesia during OE and head-up Table 1 Patient characteristics for patients undergoing robot- assisted hybrid (RE) or open esophagectomy (OE) tilt and abdominal CO2 insufflation during RE. We hy- n n P pothesized that plasma proANP would decrease when RE ( = 25) OE ( = 25) -value CBV is compromised during the abdominal part of RE Age, years 64.8 (±10.4) 68 (±7.9) 0.1 and that a positive fluid balance would be required to Male sex, n (%) 22 (88.0) 20 (80.0) 0.5 maintain plasma proANP when fluid administration is BMI, kg/m2 25.2 (±3.3) 25.8 (±5.1) 0.15 based mainly on LR. Alcohol, earlier abuse, n (%) 3 (12.0) 2 (8.0) 1.0 Tobacco, current & former, n (%) 22 (88.0) 22 (88.0) 1.0 Methods ≥ n This prospective non-randomized study was a secondary ASA-classification 3, (%) 5 (20.0) 12 (48) 0.04 data analysis of a clinical trial directed to monitor gastric Hypercholesterolemia, n (%) 1 (4.0) 7 (28.0) 0.03 microcirculation during RE and OE esophagectomy Hypertension, n (%) 10 (40.0) 12 (48.0) 0.6 (ClinicalTrials.gov, ID: NCT02077673) [14] as approved Diabetes, n (%) 5 (20.0) 8 (32.0) 0.4 by the Scientific Ethical Committees, Capital Region, Heart disease, n (%) 1 (4.0) 3 (12.0) 0.7 Denmark (H-2-2013-101). Patients were consecutively Pulmonary disease, n (%) 1 (4.0) 5 (20.0) 0.1 included between December 2013 and April 2015. Oral and written informed consent was provided at least Duration of procedure, minutes 254 (±34.0) 239 (±41.0) 0.9 1 day before surgery. All patients with biopsy verified LOS, days 13 (±7.0) 15 (±8.0) 0.3 adenocarcinoma of the gastroesophageal junction eli- BMI body mass index, ASA American Society of Anesthesiologists classification, LOS length of hospital stay. Heart disease: ischemic heart disease, arrhythmias, gible for a two-stage procedure with an abdominal and a and valve insufficiency. P-values by univariate analyses. Values are mean with thoracic part (Ivor Lewis esophagectomy) [15] were standard deviation (SD) unless stated otherwise Strandby et al. BMC Anesthesiology (2017) 17:20 Page 3 of 7 Table 2 Perioperative fluid administration during open (OE) and region of the precursor [17] and is validated with excel- robot-assisted esophagectomy (RE) lent performance in non-heart failure patients against a OE (n = 25) RE (n = 25) P-value gold standard immunoassay [18–20]. Fluid administration, mla 2600 (2400–3166) 2500 (2150–2825) 0.2 Electrolytes, mlb 1993 (1725–2475) 2000 (1700–2300) 0.7 Statistics Statistics was carried out by IBM SPSS® version 22.0.0 Human albumin, Voluven 500 (500–938) 500 (250–750) 0.2 & PRBC, ml (SPSS, Inc., IL, USA) and graphs constructed (Graph Ephedrine, mg 2.5 (0–14) 5.0 (0–13) 0.9 Pad Software Inc., CA, USA). Baseline characteristics were evaluated with chi-square or Fisher’s exact test for Phenylephrine, mg 0.1 (0–0.3) 0.2 (0–0.4) 0.9 nominal variables and t-test and Mann–Whitney U-test – – Vasopressor infusion, 0.14 (0.1 0.2) 0.12 (0.1 0.2) 0.6 for continuous variables depending on whether data ml/min were normally distributed.