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Pathophysiology and clinical implications of perioperative fluid excess

2002; Elsevier BV; Volume: 89; Issue: 4 Linguagem: Inglês

10.1093/bja/aef220

1471-6771

Kathrine Holte, Nigel E. Sharrock, Henrik Kehlet,

Abdominal Surgery and Complications

The practice of perioperative fluid therapy is variable, ranging from ‘high volume’ to ‘dry’ regimen. A review of the data on the effect of ‘high volume’ perioperative fluid therapy suggests that the resulting overhydration may have deleterious effects on cardiac and pulmonary function, and on recovery of gastrointestinal motility (postoperative ileus), tissue oxygenation, wound healing and coagulation. These observations call for randomized studies of the effects of ‘high’ vs ‘low’ volume replacement therapy on postoperative morbidity, in order to establish evidence-based guidelines for perioperative fluid management. Perioperative fluid replacement has been, and still is, the focus of much debate. This debate has primarily focused on the various types of fluid components available for replacement therapy, and not on the actual amount of fluid administered. The principles of perioperative fluid therapy were fostered in the late 1950s and early 1960s. Recom mendations for restricted fluid regimen came primarily from Francis Moore,85Moore FD Metabolic Care of the Surgical Patient. WB Saunders Co., Philadelphia1959Google Scholar arguing that the net effect of the obligatory metabolic–endocrine response to trauma, which is conservation of water and sodium, implied restriction in fluid delivery. In contrast, Tom Shires129Shires T Williams J Brown F Acute change in extracellular fluids associated with major surgical procedures.Ann Surg. 1961; 154: 803-810Crossref PubMed Google Scholar postulated a decrease in extracellular volume after surgery, due to internal redistribution of fluids, the ‘third space’ losses, and advocated replacement of these losses by additional fluid infusion. These considerations were supported by studies during the Korean War, where large amounts of fluid were administered in trauma patients with improved survival, thereby also influencing the recommendations for elective surgery.6Artz Clinical observations on the use of dextran and modified fluid gelatin in combat casualties.Surgery. 1955; 37: 612-621PubMed Google Scholar The concept of resuscitation in order to achieve supranormal circulatory function was developed in the 1970s and 1980s by Shoemaker,130Shoemaker WC Appel P Bland R Use of physiologic monitoring to predict outcome and to assist in clinical decisions in critically ill postoperative patients.Am J Surg. 1983; 146: 43-50Abstract Full Text PDF PubMed Scopus (98) Google Scholar and obtained primarily by the use of fluid infusions and inotropes. Clinical practice has largely been influenced by Shires’ recommendations and it has not been uncommon to see very large amounts of fluid administered in elective surgical procedures, way in excess of the actual losses. This is especially the case in major aortic or abdominal surgery, where 4–6 litres or more of intraoperative fluid substitution (apart from replacement of blood losses) have been given,22Cohn LH Powell MR Seidlitz L Hamilton WK Wylie EJ Fluid requirements and shifts after reconstruction of the aorta.Am J Surg. 1970; 120: 182-186Abstract Full Text PDF PubMed Google Scholar 35Garnett RL MacIntyre A Lindsay P et al.Perioperative ischaemia in aortic surgery: combined epidural/general anaesthesia and epidural analgesia vs general anaesthesia and i.v. analgesia.Can J Anaesth. 1996; 43: 769-777Crossref PubMed Scopus (0) Google Scholar 66Lang K Boldt J Suttner S Haisch G Colloids versus crystalloids and tissue oxygen tension in patients undergoing major abdominal surgery.Anesth Analg. 2001; 93: 405-409PubMed Google Scholar 134Thompson JE Vollman RW Austin DJ Kartchner MM Prevention of hypotensive and renal complications of aortic surgery using balanced salt solution: thirteen-year experience with 670 cases.Ann Surg. 1968; 167: 767-777Crossref PubMed Google Scholar or in peripheral vascular surgery with more than 6 litres of fluid administered within surgery and the first 24 h after surgery, despite a minimal blood loss.19Christopherson R Beattie C Frank SM et al.Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery.Anesthesiology. 1993; 79: 422-434Crossref PubMed Google Scholar Up to 4 litres of fluid have been administered within the first 24 h in patients undergoing laparoscopic cholecystectomy.36Glaser F Sannwald GA Buhr HJ et al.General stress response to conventional and laparoscopic cholecystectomy.Ann Surg. 1995; 221: 372-380Crossref PubMed Google Scholar In contrast, in thoracic surgery, relatively ‘dry’ regimen have been considered to be beneficial, due to the association between the amount of administered fluid and the development of post-pneumonectomy pulmonary oedema.52Jordan S Mitchell JA Quinlan GJ Goldstraw P Evans TW The pathogenesis of lung injury following pulmonary resection.Eur Respir J. 2000; 15: 790-799Crossref PubMed Scopus (161) Google Scholar 133Slinger PD Perioperative fluid management for thoracic surgery: the puzzle of postpneumonectomy pulmonary edema.J Cardiothorac Vasc Anesth. 1995; 9: 442-451Abstract Full Text PDF PubMed Scopus (0) Google Scholar 149Zeldin RA Normandin D Landtwing D Peters RM Postpneumonectomy pulmonary edema.J Thorac Cardiovasc Surg. 1984; 87: 359-365Abstract Full Text PDF PubMed Google Scholar Several issues in perioperative management may account for the administration of excessive amounts of fluid, including concern about preoperative fluid deficits (dehydration, primarily derived from prolonged preoperative fasting and bowel preparation), attempts to support the circulation and cardiac function after general and regional anaesthesia, attempts to control the circulation postoperatively, administration of crystalloid or colloid to avoid blood transfusion, preservation of urine output and preservation of a high CVP from fluid infusion. Administration of excess fluid may cause several problems after surgery. The resulting increased demands on cardiac function, due to an excessive shift to the right on the Starling myocardial performance curve, may potentially increase postoperative cardiac morbidity. Fluid accumulation in the lungs may predispose patients to pneumonia and respiratory failure. The excretory demands of the kidney are increased, and the resulting diuresis may lead to urinary retention mediated by the inhibitory effects of anaesthetics and analgesics on bladder function. Gastrointestinal motility may be inhibited, prolonging postoperative ileus. Excess fluid may decrease tissue oxygenation with implications for wound (anastomotic) healing. Finally, coagulation may be enhanced with crystalloids, which may predispose patients to postoperative thrombosis. In this review we summarize the pathophysiology of perioperative fluid excess, and review the effects of it on organ function and the potential clinical implications. We discuss the aspects of fluid management in regional anaesthesia, and the implications of immobilization on fluid homeostasis. We focus on perioperative fluid therapy in elective surgical procedures. We do not intend to present recommendations on fluid replacement strategies, or to discuss the various components available for fluid replacement or the current methods of monitoring fluid balance. Furthermore, we do not intend to discuss the treatment options for hypovolaemia or the use of i.v. fluids in critically ill patients. Water makes up 60% of total body weight, one third of it being extracellular fluid volume (ECV) (interstitial fluid and plasma), and two thirds being intracellular volume. Transportation of fluid between the body compartments is regulated by the Starling equilibrium, the decisive variables being differences in hydrostatic and colloid osmotic pressure, and specific permeability coefficients. In response to surgery, serum colloid osmotic pressure is decreased,64Ladegaard-Pedersen HJ Postoperative changes in blood volume and colloid osmotic pressure.Acta Chir Scand. 1969; 135: 94-104PubMed Google Scholar 125Shippy CR Shoemaker WC Hemodynamic and colloid osmotic pressure alterations in the surgical patient.Crit Care Med. 1983; 11: 191-195Crossref PubMed Google Scholar which is primarily caused by increased capillary permeability, resulting in fluid shifts from the vascular bed to the interstitial fluid.60Kongstad L Moller AD Grande PO Reflection coefficient for albumin and capillary fluid permeability in cat calf muscle after traumatic injury.Acta Physiol Scand. 1999; 165: 369-377Crossref PubMed Scopus (0) Google Scholar 125Shippy CR Shoemaker WC Hemodynamic and colloid osmotic pressure alterations in the surgical patient.Crit Care Med. 1983; 11: 191-195Crossref PubMed Google Scholar Dilution secondary to crystalloid infusions may also contribute.71Lobo DN Stanga Z Simpson JA Anderson JA Rowlands BJ Allison SP Dilution and redistribution effects of rapid 2-litre infusions of 0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in normal subjects: a double-blind crossover study.Clin Sci (Lond). 2001; 101: 173-179Crossref PubMed Scopus (0) Google Scholar In addition, as a physiological response to a decrease in intravascular pressure, fluid movement from the extravascular to the intravascular space occurs, as demonstrated in a human volunteer study where experimental hypovolaemia led to fluid movements from tissue to blood.74Lundvall J Lanne T Large capacity in man for effective plasma volume control in hypovolaemia via fluid transfer from tissue to blood.Acta Physiol Scand. 1989; 137: 513-520Crossref PubMed Google Scholar Changes in ECV after surgery have been much debated, and fluid replacement today is greatly influenced by Shires,127Shires GT Carrico J Lightfoot S Fluid therapy in hemorrhagic shock.Arch Surg. 1964; 88: 688-693Crossref PubMed Scopus (252) Google Scholar 129Shires T Williams J Brown F Acute change in extracellular fluids associated with major surgical procedures.Ann Surg. 1961; 154: 803-810Crossref PubMed Google Scholar who postulated a decrease in functional (i.e. exchangeable) ECV after elective surgical procedures and haemorrhagic shock. According to Shires, surgical trauma per se (without administration of fluids) led to a decrease in functional ECV, which was proportional to the degree of surgical trauma.129Shires T Williams J Brown F Acute change in extracellular fluids associated with major surgical procedures.Ann Surg. 1961; 154: 803-810Crossref PubMed Google Scholar Shires primarily explained the decrease in functional ECV by sequestration of fluids within the traumatized area or expansion of the intracellular volume, and therefore advocated replacement of these losses with additional saline infusions.110Roberts JP Roberts JD Skinner C Shires GT Illner H Canizaro PC Extracellular fluid deficit following operation and its correction with Ringer's lactate. A reassessment.Ann Surg. 1985; 202: 1-8Crossref PubMed Google Scholar 128Shires GT Jackson DE Postoperative salt tolerance.Arch Surg. 1962; 84: 703-709Crossref PubMed Google Scholar 129Shires T Williams J Brown F Acute change in extracellular fluids associated with major surgical procedures.Ann Surg. 1961; 154: 803-810Crossref PubMed Google Scholar However, these observations have been contradicted by several other investigators reporting unchanged,40Gutelius JR Shizgal HM Lopez G The effect of trauma on extracellular water volume.Arch Surg. 1968; 97: 206-214Crossref PubMed Google Scholar 65Ladegaard-Pedersen HJ Engell HC A comparison between the changes in the distribution volumes of inulin and [51Cr]EDTA after major surgery.Scand J Clin Lab Invest. 1975; 35: 109-113Crossref PubMed Google Scholar 91Nielsen OM Engell HC Extracellular fluid volume and distribution in relation to changes in plasma colloid osmotic pressure after major surgery. A randomized study.Acta Chir Scand. 1985; 151: 221-225PubMed Google Scholar 138Virtue RW LeVine DS Aikawa JK Fluid shifts during the surgical period: RISA and S35 determinations following glucose, saline or lactate infusion.Ann Surg. 1966; 163: 523-528Crossref PubMed Google Scholar or even increased,21Cleland J Pluth JR Tauxe WN Kirklin JW Blood volume and body fluid compartment changes soon after closed and open intracardiac surgery.J Thorac Cardiovasc Surg. 1966; 52: 698-705Abstract Full Text PDF PubMed Google Scholar 112Roth E Lax LC Maloney JV Ringer's lactate solution and extracellular fluid volume in the surgical patient: a critical analysis.Ann Surg. 1969; 169: 149-164Crossref PubMed Google Scholar ECV in postoperative patients, and studies in major surgery suggest that ECV expansion may correlate with intraoperative fluid administration.93Nielsen OM Engell HC The importance of plasma colloid osmotic pressure for interstitial fluid volume and fluid balance after elective abdominal vascular surgery.Ann Surg. 1986; 203: 25-29Crossref PubMed Google Scholar 112Roth E Lax LC Maloney JV Ringer's lactate solution and extracellular fluid volume in the surgical patient: a critical analysis.Ann Surg. 1969; 169: 149-164Crossref PubMed Google Scholar Thus, a positive fluid balance of 3 litres was associated with unchanged ECV, but a smaller or larger fluid excess with a decrease or increase in ECV, respectively.93Nielsen OM Engell HC The importance of plasma colloid osmotic pressure for interstitial fluid volume and fluid balance after elective abdominal vascular surgery.Ann Surg. 1986; 203: 25-29Crossref PubMed Google Scholar In other studies, intracellular volume has been found to be decreased after surgery (intracellular dehydration).31Finn PJ Plank LD Clark MA Connolly AB Hill GL Progressive cellular dehydration and proteolysis in critically ill patients.Lancet. 1996; 347: 654-656Abstract PubMed Scopus (0) Google Scholar Difficulty in obtaining accurate measurements of the fluid phases is generally recognized,86Moore FD Shires G Moderation.Ann Surg. 1967; 166: 300-301Crossref PubMed Google Scholar however, and may relate to the use of isotopes with different volumes of distribution, different equilibrium times and general changes in equilibrium times and distribution volumes as a consequence of the surgical trauma. Therefore, despite 30 yr of research, perioperative ECV changes have not been clarified. However, the present data suggest that the magnitude of ECV decrease suggested by Shires may not be accurate, partly because the type of surgery, anaesthesia and perioperative fluid management were not standardized. Further studies are required to assess ECV changes after surgery with standardized regimen. Surgery elicits a stress response of combined endocrine and inflammatory origin.27Desborough JP The stress response to trauma and surgery.Br J Anaesth. 2000; 85: 109-117Crossref PubMed Google Scholar 143Wilmore DW Metabolic response to severe surgical illness: overview.World J Surg. 2000; 24: 705-711Crossref PubMed Scopus (103) Google Scholar Several of the hormones involved in this response may exert a potentially profound influence on the distribution of body fluids (Table 1). Generally, the endocrine response to surgical trauma leads to conservation of sodium and water and to excretion of potassium, the principal mediators being antidiuretic hormone (ADH), aldosterone and the renin–angiotensin II system.27Desborough JP The stress response to trauma and surgery.Br J Anaesth. 2000; 85: 109-117Crossref PubMed Google Scholar 143Wilmore DW Metabolic response to severe surgical illness: overview.World J Surg. 2000; 24: 705-711Crossref PubMed Scopus (103) Google Scholar The increased ADH secretion leads to enhanced water reabsorption in the kidney, resulting in a postoperative decrease in diuresis and a decrease in plasma concentrations of sodium. The increased secretion of aldosterone and renin leads to conservation of sodium and excretion of potassium. Several other mediators, enhanced by the surgical stress, may influence the distribution of fluid. Thus, increased cortisol secretion, an obligatory stress response, may be of major importance in the control fluid homeostasis, primarily through permissive actions to maintain capillary integrity.117Sapolsky RM Romero LM Munck AU How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.Endocr Rev. 2000; 21: 55-89Crossref PubMed Scopus (3540) Google Scholar In addition, the cortisol-induced inhibition of excessive inflammatory activity response to trauma may reduce postoperative fluid shifts.117Sapolsky RM Romero LM Munck AU How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.Endocr Rev. 2000; 21: 55-89Crossref PubMed Scopus (3540) Google Scholar Atrial natriuretic peptide (ANP) secretion in response to surgery is unclear because ANP secretion may be increased in older patients, in contrast to unchanged ANP levels in younger patients.59Kidd JE Gilchrist NL Utley RJ Nicholls MG Espiner EA Yandle TG Effect of opiate, general anaesthesia and surgery on plasma atrial natriuretic peptide levels in man.Clin Exp Pharmacol Physiol. 1987; 14: 755-760Crossref PubMed Google Scholar 62Kudoh A Ishihara H Matsuki A Renin-aldosterone system and atrial natriuretic peptide during anesthesia in orthopedic patients over 80 years of age.J Clin Anesth. 1999; 11: 101-107Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar 63Kudoh A Sakai T Ishihara H Matsuki A Renin-aldosterone in elderly patients with hyperkalaemia under anaesthesia.Eur J Anaesthesiol. 1999; 16: 231-235Crossref PubMed Scopus (3) Google Scholar ANP may induce natriuresis, diuresis and inhibition of aldosterone and ADH secretion.90Needleman P Greenwald JE Atriopeptin: a cardiac hormone intimately involved in fluid, electrolyte, and blood-pressure homeostasis.N Engl J Med. 1986; 314: 828-834Crossref PubMed Google Scholar Further more, inflammatory mediators, like IL-6, TNF, substance-P and bradykinin may act as vasodilators and increase capillary permeability. The release of these inflammatory mediators is proportional to the magnitude of the surgical trauma.58Kehlet H Surgical stress response: does endoscopic surgery confer an advantage?.World J Surg. 1999; 23: 801-807Crossref PubMed Scopus (0) Google Scholar The hormonal release in response to surgical trauma therefore generally induces a shift toward water and sodium retention, while the excretion of potassium is increased, paralleling the increase in catabolism.Table 1Hormonal responses to surgery and fluid overloadHormoneResponse to surgeryResponse to overloadEffect on fluid distribution(Reference numbers)AldosteroneIncrease (27Desborough JP The stress response to trauma and surgery.Br J Anaesth. 2000; 85: 109-117Crossref PubMed Google Scholar, 143Wilmore DW Metabolic response to severe surgical illness: overview.World J Surg. 2000; 24: 705-711Crossref PubMed Scopus (103) Google Scholar)Decrease (142Williams GH Duhly RG Hypertensive states: associated fluid and electrolyte disturbances.in: Narins RG Maxwell and Kleman's Clinical Disorder of Fluid and Electrolyte Metabolism. 5th Edn. McGraw-Hill, New York1994: 1619-1648Google Scholar)Sodium and fluid retention; potassium excretionAntidiuretic hormoneIncrease (27Desborough JP The stress response to trauma and surgery.Br J Anaesth. 2000; 85: 109-117Crossref PubMed Google Scholar, 143Wilmore DW Metabolic response to severe surgical illness: overview.World J Surg. 2000; 24: 705-711Crossref PubMed Scopus (103) Google Scholar)Decrease (48Ishihara H Ishida K Oyama T Kudo T Kudo M Effects of general anaesthesia and surgery on renal function and plasma ADH levels.Can Anaesth Soc J. 1978; 25: 312-318Crossref PubMed Google Scholar)Water retentionRenin–angiotensin IIIncrease (27Desborough JP The stress response to trauma and surgery.Br J Anaesth. 2000; 85: 109-117Crossref PubMed Google Scholar, 143Wilmore DW Metabolic response to severe surgical illness: overview.World J Surg. 2000; 24: 705-711Crossref PubMed Scopus (103) Google Scholar)Decrease (2–4, 94, 142Williams GH Duhly RG Hypertensive states: associated fluid and electrolyte disturbances.in: Narins RG Maxwell and Kleman's Clinical Disorder of Fluid and Electrolyte Metabolism. 5th Edn. McGraw-Hill, New York1994: 1619-1648Google Scholar)Sodium and fluid retention; potassium excretionAtrial natriuretic peptideIncrease or no change (59Kidd JE Gilchrist NL Utley RJ Nicholls MG Espiner EA Yandle TG Effect of opiate, general anaesthesia and surgery on plasma atrial natriuretic peptide levels in man.Clin Exp Pharmacol Physiol. 1987; 14: 755-760Crossref PubMed Google Scholar, 62Kudoh A Ishihara H Matsuki A Renin-aldosterone system and atrial natriuretic peptide during anesthesia in orthopedic patients over 80 years of age.J Clin Anesth. 1999; 11: 101-107Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 63Kudoh A Sakai T Ishihara H Matsuki A Renin-aldosterone in elderly patients with hyperkalaemia under anaesthesia.Eur J Anaesthesiol. 1999; 16: 231-235Crossref PubMed Scopus (3) Google Scholar)Increase (54Kamp-Jensen M Olesen KL Bach V Schutten HJ Engquist A Changes in serum electrolyte and atrial natriuretic peptide concentrations, acid–base and haemodynamic status after rapid infusion of isotonic saline and Ringer lactate solution in healthy volunteers.Br J Anaesth. 1990; 64: 606-610Crossref PubMed Scopus (0) Google Scholar, 68Lewis H Wilkins M Selwyn B Yelland U Griffith M Bhoola KD Relationship between ANP, cyclic GMP and tissue kallikrein following saline infusion in healthy volunteers.Adv Exp Med Biol. 1989; 247A: 281-286PubMed Google Scholar, 119Schutten HJ Johannessen AC Torp-Pedersen C Sander-Jensen K Bie P Warberg J Central venous pressure—a physiological stimulus for secretion of atrial natriuretic peptide in humans?.Acta Physiol Scand. 1987; 131: 265-272Crossref PubMed Google Scholar, 146Yamaji T Ishibashi M Takaku F Atrial natriuretic factor in human blood.J Clin Invest. 1985; 76: 1705-1709Crossref PubMed Google Scholar)Diuretic; natriuretic Open table in a new tab Studies in healthy volunteers make it possible to investigate the individual factors of importance in perioperative fluid balance, independently of the surgical trauma; the surgically induced factors, such as increased capillary permeability, are eliminated when studying volunteers. In order to investigate the effects of the stress responses seen after surgery per se, continuous infusions (>2 days) of cortisol/hydrocortisone, glucagon and epinephrine have, in three studies in healthy volunteers, been found to decrease sodium excretion and increase potassium excretion.10Bessey PQ Lowe KA Early hormonal changes affect the catabolic response to trauma.Ann Surg. 1993; 218: 476-489Crossref PubMed Google Scholar 11Bessey PQ Watters JM Aoki TT Wilmore DW Combined hormonal infusion simulates the metabolic response to injury.Ann Surg. 1984; 200: 264-281Crossref PubMed Google Scholar 140Watters JM Bessey PQ Dinarello CA Wolff SM Wilmore DW Both inflammatory and endocrine mediators stimulate host responses to sepsis.Arch Surg. 1986; 121: 179-190Crossref PubMed Google Scholar Furthermore, in two of these studies a weight gain of approximately 0.4 and 1.7 kg, respectively, was seen.11Bessey PQ Watters JM Aoki TT Wilmore DW Combined hormonal infusion simulates the metabolic response to injury.Ann Surg. 1984; 200: 264-281Crossref PubMed Google Scholar 140Watters JM Bessey PQ Dinarello CA Wolff SM Wilmore DW Both inflammatory and endocrine mediators stimulate host responses to sepsis.Arch Surg. 1986; 121: 179-190Crossref PubMed Google Scholar These findings were not modified by the concomitant infusion of an inflammatory agent (ethiocholanolone),140Watters JM Bessey PQ Dinarello CA Wolff SM Wilmore DW Both inflammatory and endocrine mediators stimulate host responses to sepsis.Arch Surg. 1986; 121: 179-190Crossref PubMed Google Scholar despite an increased acute phase protein response. These results demonstrate that activation of the stress response leads to fluid retention. In contrast, several of the stress responses to injury may be influenced by fluid volume expansion per se. Increased capillary permeability leading to increased filtration of plasma proteins was seen after infusion of Dextran 1000 ml or 360 ml of albumin in healthy volunteers.96Parving HH Rossing N Nielsen SL Lassen NA Increased transcapillary escape rate of albumin, IgG, and IgM after plasma volume expansion.Am J Physiol. 1974; 227: 245-250PubMed Google Scholar The inhibition of aldosterone secretion with fluid infusions is well established, both in healthy volunteers and surgical patients.142Williams GH Duhly RG Hypertensive states: associated fluid and electrolyte disturbances.in: Narins RG Maxwell and Kleman's Clinical Disorder of Fluid and Electrolyte Metabolism. 5th Edn. McGraw-Hill, New York1994: 1619-1648Google Scholar Attenuation of ADH secretion seems only to occur with high volume fluid infusions of about 50 ml min−1,48Ishihara H Ishida K Oyama T Kudo T Kudo M Effects of general anaesthesia and surgery on renal function and plasma ADH levels.Can Anaesth Soc J. 1978; 25: 312-318Crossref PubMed Google Scholar while lower infusion volumes of 15 ml min−1 12Bonnet F Harari A Thibonnier M Viars P Suppression of antidiuretic hormone hypersecretion during surgery by extradural anaesthesia.Br J Anaesth. 1982; 54: 29-36Crossref PubMed Scopus (0) Google Scholar or 15 ml kg−1 h−1 132Sinnatamby C Edwards CR Kitau Irving MH Antidiuretic hormone response to high and conservative fluid regimes in patients undergoing operation.Surg Gynecol Obstet. 1974; 139: 715-719PubMed Google Scholar did not attenuate it. ANP secretion is increased after saline infusion in healthy volunteers,54Kamp-Jensen M Olesen KL Bach V Schutten HJ Engquist A Changes in serum electrolyte and atrial natriuretic peptide concentrations, acid–base and haemodynamic status after rapid infusion of isotonic saline and Ringer lactate solution in healthy volunteers.Br J Anaesth. 1990; 64: 606-610Crossref PubMed Scopus (0) Google Scholar 68Lewis H Wilkins M Selwyn B Yelland U Griffith M Bhoola KD Relationship between ANP, cyclic GMP and tissue kallikrein following saline infusion in healthy volunteers.Adv Exp Med Biol. 1989; 247A: 281-286PubMed Google Scholar 119Schutten HJ Johannessen AC Torp-Pedersen C Sander-Jensen K Bie P Warberg J Central venous pressure—a physiological stimulus for secretion of atrial natriuretic peptide in humans?.Acta Physiol Scand. 1987; 131: 265-272Crossref PubMed Google Scholar 146Yamaji T Ishibashi M Takaku F Atrial natriuretic factor in human blood.J Clin Invest. 1985; 76: 1705-1709Crossref PubMed Google Scholar but the response is transient and occurs within and immediately after the infusion. The renin–angiotensin II secretion is inhibited with fluid administration, and evidence suggests that the renin–angiotensin II system is of major importance in the excretion of a fluid overload.2Andersen LJ Jensen TU Bestle MH Bie P Isotonic and hypertonic sodium loading in supine humans.Acta Physiol Scand. 1999; 166: 23-30Crossref PubMed Scopus (27) Google Scholar, 3Andersen LJ Jensen TU Bestle MH Bie P Gastrointestinal osmoreceptors and renal sodium excretion in humans.Am J Physiol Regul Integr Comp Physiol. 2000; 278: R287-R294PubMed Google Scholar, 4Andersen LJ Norsk P Johansen LB Christensen P Engstrom T Bie P Osmoregulatory control of renal sodium excretion after sodium loading in humans.Am J Physiol. 1998; 275: R1833-R1842PubMed Google Scholar 29Drummer C Gerzer R Heer M et al.Effects of an acute saline infusion on fluid and electrolyte metabolism in humans.Am J Physiol. 1992; 262: F744-F754PubMed Google Scholar 94Norsk P Drummer C Rocker L et al.Renal and endocrine responses in humans to isotonic saline infusion during microgravity.J Appl Physiol. 1995; 78: 2253-2259Crossref PubMed Scopus (0) Google Scholar 142Williams GH Duhly RG Hypertensive states: associated fluid and electrolyte disturbances.in: Narins RG Maxwell and Kleman's Clinical Disorder of Fluid and Electrolyte Metabolism. 5th Edn. McGraw-Hill, New York1994: 1619-1648Google Scholar However, there is no systematic evaluation of ANP and renin responses to fluid regimen in surgical procedures. A large fluid volume therefore influences several of the hormonal responses to injury in surgical patients (decrease in ADH, decrease in aldosterone), while the effect of fluid administration on other hormones known to be increased postoperatively (renin and ANP) has only been systematically evaluated in healthy volunteers. Thus, the effects of perioperative fluid administration on the stress responses to surgery are unclear and need to be evaluated in clinical studies comparing high vs low fluid regimen. The physiological relationship between cardiac filling and cardiac output is described in Starling's myocardial performance curve (Fig. 1). The curve describes the functional consequences of alterations in preload on cardiac output, and is the rationale behind improvement of cardiac output by volume administration. Until a certain point, volume expansion leads to increased cardiac output due to increased end-diastolic ventricular filling. Beyond that point, increased end-diastolic volume will lead to a decrease in cardiac output due to depression of ventricular function. Measurements of cardiac responses (primarily cardiac output) in response to a fluid load have been used to define the optimal ventricular filling pressures (evaluated by pulmonary artery catheter measurements).15Bush HL LoGerfo FW Weisel RD Mannick JA Hechtman HB Assessment of myocardial performance and optimal volume loading during elective abdominal aortic aneurysm resection.Arch Surg. 1977; 112: 1301-1305Crossref PubMed Google Scholar 77Manny J Grindlinger GA Dennis RC Weisel RD Hechtman HB Myocardial performance