The HYSLAR Trial: A Prospective Randomized Controlled Trial of the Use of a Restrictive Fluid Regimen With 3% Hypertonic Saline Versus Lactated Ringers in Patients Undergoing Pancreaticoduodenectomy

Objective:This study was designed to determine whether the volume and type of fluid administered for pancreaticoduodenectomy impacts postoperative outcomes. Background:Three percent hypertonic saline (HYS) has been suggested as a means of reducing the volume of fluid required to sustain tissue perfusion in the perioperative period. Methods:Between May 2011 and November 2013, patients undergoing pancreaticoduodenectomy were enrolled in an institutional review board–approved, single-center, prospective, parallel, randomized controlled trial (NCT 01428050), comparing lactated Ringers (LAR) (15 mL/kg/hr LAR intraoperation, 2 mL/kg/hr LAR postoperation) with HYS (9 mL/kg/hr LAR and 1 mL/kg/hr HYS intraoperation, 1 mL/kg/hr HYS postoperation). Results:A total of 264 patients were randomized. Demographic variables between groups were similar. The HYS patients had a significantly reduced net fluid balance (65 vs 91 mL/kg, P = 0.02). The overall complication rate was reduced in the HYS group (43% vs 54%), with a relative risk of 0.79 [95% confidence interval (CI), 0.62–1.02; P = 0.073], factoring stratification for pancreas texture. After adjustment for age and weight, the relative risk was 0.75 [95% CI (0.58–0.96); P = 0.023]. The total number of complications was significantly reduced in the HYS group (93 vs 123), with an incidence rate ratio of 0.74 [95% CI (0.56–0.97); P = 0.027]. After adjustment for age and weight, the incidence rate ratio was 0.69 [95% CI (0.52–0.90); P = 0.0068]. Reoperations, length of stay, readmissions, and 90-day mortality were similar between groups. Conclusions:A moderately restrictive fluid regimen with HYS resulted in a statistically significant 25% reduction in complications when adjusted for age, weight, and pancreatic texture.

[1]  M. Werner,et al.  Intraoperative crystalloid overload leads to substantial inflammatory infiltration of intestinal anastomoses-a histomorphological analysis. , 2013, Surgery.

[2]  A. Chernyavskiy,et al.  Hypertonic solution decreases extravascular lung water in cardiac patients undergoing cardiopulmonary bypass surgery. , 2013, Journal of cardiothoracic and vascular anesthesia.

[3]  M. Gonen,et al.  Intraoperative fluid management and complications following pancreatectomy , 2013, Journal of surgical oncology.

[4]  A. Zaborin,et al.  Intestinal Tissues Induce an SNP Mutation in Pseudomonas aeruginosa That Enhances Its Virulence: Possible Role in Anastomotic Leak , 2012, PloS one.

[5]  A. Ropper.  Hyperosmolar therapy for raised intracranial pressure. , 2012, The New England journal of medicine.

[6]  B. Leiby,et al.  Perioperative surgical care bundle reduces pancreaticoduodenectomy wound infections. , 2012, The Journal of surgical research.

[7]  M. Gonen,et al.  Relationship Between Intraoperative Fluid Administration and Perioperative Outcome After Pancreaticoduodenectomy: Results of a Prospective Randomized Trial of Acute Normovolemic Hemodilution Compared With Standard Intraoperative Management , 2010, Annals of surgery.

[8]  Martin H. Dauber,et al.  Miller’s Anesthesia , 2010 .

[9]  D. Moher,et al.  CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials , 2010, BMJ : British Medical Journal.

[10]  K. Burns,et al.  Hypertonic saline for peri-operative fluid management. , 2010, The Cochrane database of systematic reviews.

[11]  C. Yeo,et al.  Reconstruction Following the Pylorus Preserving Whipple Resection: PJ, HJ, and DJ , 2010, Journal of Gastrointestinal Surgery.

[12]  K. Lillemoe,et al.  Does type of pancreaticojejunostomy after pancreaticoduodenectomy decrease rate of pancreatic fistula? A randomized, prospective, dual-institution trial. , 2009, Journal of the American College of Surgeons.

[13]  M. Koch,et al.  Meta‐analysis of standard, restrictive and supplemental fluid administration in colorectal surgery , 2009, The British journal of surgery.

[14]  Charles J. Yeo,et al.  Implementation of a Critical Pathway for Distal Pancreatectomy at an Academic Institution , 2009, Journal of Gastrointestinal Surgery.

[15]  M. Gonen,et al.  A Prospective Randomized Trial of Acute Normovolemic Hemodilution Compared to Standard Intraoperative Management in Patients Undergoing Major Hepatic Resection , 2008, Annals of surgery.

[16]  Margaret A Dudeck,et al.  CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. , 2008, American journal of infection control.

[17]  J. Alpert,et al.  Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction , 2008 .

[18]  D. Gouma,et al.  Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). , 2007, Surgery.

[19]  H. Kehlet,et al.  Liberal or restrictive fluid administration in fast-track colonic surgery: a randomized, double-blind study. , 2007, British journal of anaesthesia.

[20]  C. Yeo,et al.  Initiation of a critical pathway for pancreaticoduodenectomy at an academic institution--the first step in multidisciplinary team building. , 2007, Journal of the American College of Surgeons.

[21]  M. Gonen,et al.  Preoperative Predictors for Complications after Pancreaticoduodenectomy: Impact of BMI and Body Fat Distribution , 2007, Journal of Gastrointestinal Surgery.

[22]  Fred S Apple,et al.  Universal definition of myocardial infarction. , 2007, Journal of the American College of Cardiology.

[23]  H. Kehlet,et al.  Fluid therapy and surgical outcomes in elective surgery: a need for reassessment in fast-track surgery. , 2006, Journal of the American College of Surgeons.

[24]  D. Sargent,et al.  A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. , 2005, Surgery.

[25]  J. Neoptolemos,et al.  Postoperative pancreatic fistula: an international study group (ISGPF) definition. , 2005, Surgery.

[26]  H. Friess,et al.  Randomized clinical trial of pylorus‐preserving duodenopancreatectomy versus classical Whipple resection—long term results , 2005, The British journal of surgery.

[27]  R. Bellomo,et al.  Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group , 2004, Critical care.

[28]  L. Tamer,et al.  N-Acetylcysteine inhibits peroxynitrite-mediated damage in oleic acid-induced lung injury , 2004, Pulmonary pharmacology & therapeutics.

[29]  Y. Mintz,et al.  Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. , 2003, Annals of surgery.

[30]  F. Pott,et al.  Effects of Intravenous Fluid Restriction on Postoperative Complications: Comparison of Two Perioperative Fluid Regimens: A Randomized Assessor-Blinded Multicenter Trial , 2003, Annals of surgery.

[31]  N. Aaronson,et al.  Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial , 2003, Gut.

[32]  K. Fearon,et al.  Supplemental perioperative fluid administration increases tissue oxygen pressure. , 2003, Surgery.

[33]  D. Lobo,et al.  Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial , 2002, The Lancet.

[34]  D. Coit,et al.  Prospective Randomized Clinical Trial of the Value of Intraperitoneal Drainage After Pancreatic Resection , 2001, Annals of surgery.

[35]  J. Boldt,et al.  Colloids versus crystalloids and tissue oxygen tension in patients undergoing major abdominal surgery. , 2001, Anesthesia and analgesia.

[36]  D. Rattner,et al.  Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization. , 2001, Archives of surgery.

[37]  M. Braga,et al.  Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition , 2001, Critical care medicine.

[38]  K. Lillemoe,et al.  Resected adenocarcinoma of the pancreas— 616 patients: Results, outcomes, and prognostic indicators , 2000, Journal of Gastrointestinal Surgery.

[39]  K. Lillemoe,et al.  Quality of life and outcomes after pancreaticoduodenectomy. , 2000, Annals of surgery.

[40]  J. Melendez,et al.  Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction. , 1998, Journal of the American College of Surgeons.

[41]  K. Lillemoe,et al.  Importance of hospital volume in the overall management of pancreatic cancer. , 1998, Annals of surgery.

[42]  Jeffrey E. Lee,et al.  Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. , 1997, Annals of surgery.

[43]  N. Black.  CONSORT , 1996, The Lancet.

[44]  G. Kramer,et al.  Fluid compartments in hemorrhaged rats after hyperosmotic crystalloid and hyperoncotic colloid resuscitation. , 1996, The American journal of physiology.

[45]  R. M. Peters,et al.  Hypertonic sodium lactate versus lactated ringer's solution for intravenous fluid therapy in operations on the abdominal aorta. , 1983, Surgery.

[46]  Rabbi Amos Edelheit.  Moderation , 1960, Philosophy of Science.