Urologic Oncology: Seminars and Original Investigations 33 (2015) 66.e21–66.e24
Original article
Improved perioperative outcome with norepinephrine and a restrictive fluid administration during open radical cystectomy and urinary diversion Patrick Y. Wuethrich, M.D.a,*, Fiona C. Burkhard, M.D.b a
Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, Bern, Switzerland b Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland Received 31 March 2014; received in revised form 22 July 2014; accepted 28 July 2014
Keywords: Postoperative outcome; Radical cystectomy; Fluid therapy; Norepinephrine
Intravenous fluid administration is fundamental in the perioperative period to replace the fluid lost during major surgery and to maintain physiological organ function. The optimal intraoperative fluid volume to be administered, however, is a matter of intense debate, and controversy persists in terms of how much fluid has to be infused, choice of fluids (crystalloids or colloids), concomitant administration of vasopressors, or a goal-directed hemodynamic therapy (GDT) aiming for an optimization or maximization of the stroke volume [1–6]. Intravenous fluids should be considered as drugs and consequently indication, timing, and dosage are relevant, regardless of the type of fluid. 1. Norepinephrine and restrictive fluid management: Less postoperative complications In 2 recent publications from a randomized clinical trial (RCT), we analyzed the impact of 2 different fluid managements on the postoperative complication rate (primary end point), intraoperative blood loss, and the packed red blood cell (PRBC) transfusion rate (secondary end points) in patients undergoing open radical cystectomy with urinary diversion. One group (norepinephrine/low volume) received a continuous norepinephrine infusion starting during the induction of anesthesia at a rate of 2 mg/kg/h combined with a restrictive deferred fluid administration (1 ml/kg/h until the bladder was removed and then 3 ml/kg/h until the end of surgery). Hypotension was corrected by adapting the norepinephrine infusion rate. This approach resulted in a Corresponding author. Tel.: þ413-1-632-2725; fax: þ416-3-205-54. E-mail address: [email protected] (P.Y. Wuethrich). *
http://dx.doi.org/10.1016/j.urolonc.2014.07.018 1078-1439/r 2014 Elsevier Inc. All rights reserved.
median crystalloid administration of 1,700 ml (range: 700– 4,000) and a median norepinephrine infusion rate of 3.6 mg/ kg/h (2.0–8.0). The other group (control) received a constant infusion rate of 6 ml/kg/h throughout surgery without norepinephrine administration. Hypotension was corrected by administering fluid boluses. This resulted in a median crystalloid administration of 4,300 ml (2,800–6,200). The overall in-hospital complication rate was significantly reduced in the norepinephrine/low-volume group (52% vs. 73%), and there was an almost a 50% reduction in the 90-day postoperative major complication rate grades III to V, according to the Clavien Dindo classification (13% vs. 25%) [7]. In our study, a zero postoperative weight gain was observed in the norepinephrine/low-volume group (Fig. 1). Postoperative body weight gain is a reliable marker of fluid overload with extravascular fluid accumulation (edema) and correlates with an increased postoperative complication and mortality rates [2,8]. This strongly suggests minimal or no clinically relevant interstitial edema formation in the norepinephrine/low-volume group with an ensuing faster return of bowel function and a reduced rate of gastrointestinal complications in this group (6% vs. 37%). Ultimately, as a consequence of the lower complication rate, the hospitalization time was significantly reduced by 2 days in the norepinephrine/low-volume group [7]. Intraoperative blood loss was decreased in the norepinephrine/low-volume group (800 vs. 1,200 ml), and interestingly the PRBC transfusion rate was reduced not only intraoperatively (8% vs. 33%) but also throughout the hospitalization (33% vs. 60%) [9]. As the number of PRBCs given may have a significant negative effect on cancer-related outcomes and overall survival in patients undergoing radical cystectomy for bladder cancer [10,11], this fact is not to be neglected.
66.e22 3
P.Y. Wuethrich, F.C. Burkhard / Urologic Oncology: Seminars and Original Investigations 33 (2015) 66.e21–66.e24 *
*
Body Weight Changes
2 1 0 -1 -2 -3
POD 1
POD2
POD3
POD4
POD5
Discharge
Fig. 1. Postoperative weight-gain (kg) differences presented as the mean with 95% CIs after radical cystectomy and urinary diversion in the 2 groups (yellow: norepinephrine/low-volume group [n ¼ 83] and purple: control group [n ¼ 83] with liberal fluid administration) (*P o 0.05, POD ¼ postoperative day). (Color version of figure is available online.)
2. Perioperative restrictive fluid management is the more physiological fluid approach Standard perioperative fluid management aims to replace basal fluid requirements, perspiration/exudation through the surgical situs, loss to the third space, blood loss, and preloading of the neuroaxial blockade. This traditional approach to fluid substitution management inevitably causes a postoperative positive fluid balance illustrated by a body weight gain on postoperative day 1. The primary explanation for this fluid overload is an overestimation of the fluid required to replace loss into the third space and through the surgical wound, which is lower than generally assumed. Insensible perspiration is around 0.5 ml/kg/h in the normal condition and increases to a maximum of 1 ml/kg/h intraoperatively [12]. The loss into the third space is questionable and most likely does not exist [13]. Fluid volume substitution according to textbook recommendations of 10 to 15 ml/kg/h for major intra-abdominal surgery is not evidence based and is increasingly being challenged [1,2,14]. In a multicenter RCT evaluating a restrictive fluid management during colorectal surgery, a zero weight gain postoperatively resulted in a faster return of gastrointestinal function, reduced postoperative complications, and a shorter hospitalization. In addition, fluid overload was shown to decrease pulmonary function and lead to pulmonary edema [2,14]. A further study showed that preemptive preloading fluid administration during neuroaxial blockade is not effective, as it does not prevent anesthesia-related hypotension [15] and inevitably results in fluid overload and postoperative weight gain. Another issue is the idea that a generous intraoperative fluid administration maintains systemic blood pressure and protects organ function, especially renal function. However, liberal fluid administration has not been shown to decrease the incidence of acute renal failure. Basically, urinary output is reduced perioperatively as a result of a stress reaction with activation of the antidiuretic hormone, aldosterone, and the renin-angiotensin II system. Increased antidiuretic hormone
secretion enhances renal water reabsorption and increased secretion of aldosterone and renin leads to conservation of sodium and excretion of potassium. Consequently, patients have a decreased urinary output and a tendency to retain fluid because administered fluids are not readily excreted, thus contributing to a postoperative fluid overload. Matot et al. [16] could demonstrate that urinary output was not affected by doubling the amount of fluid administered during thoracoscopic surgery. Intraoperative administration of α-1 and β-1 mimetics, which influence the reninangiotensin-aldosterone and the adrenergic systems, could enhance urinary output and would be beneficial [17]. Physiological, balanced crystalloid solutions (Ringer's lactate or Ringer's maleate as administered in our RCT) should be used instead of a 0.9% sodium chloride solution. Hyperchloremia and hyperchloremic metabolic acidosis can be caused by fluid resuscitation with 0.9% sodium chloride solution and consequently renal blood flow will be reduced. In addition, the administration of a balanced crystalloid solution perioperatively decreased the rate of postoperative infections, renal replacement therapy, blood transfusion, and acidosis-associated investigations compared with a 0.9% saline solution for major abdominal surgery in an observational study [18]. The need for replacement of intraoperative blood loss is evident. However, volume effects are context sensitive and different during anesthesia and surgery, as renal clearance of crystalloid fluid is only 15% to 20% of that found in healthy nonanesthetized volunteers [19]. Conventional colloid (1:1) or crystalloid (3:1) administration in proportion to the amount of blood loss can cause transient hypervolemia and promote serious rebleeding [20,21]. Acute hypervolemia can alter or destroy the endothelial surface layer (glycocalyx), which is the key structure of the vascular barrier. Transient hypervolemia due to fluid overload can induce a relevant fluid and protein shift toward the interstitium, resulting in interstitial edema with the ensuing negative effects on bowel function. Colloids are not superior to crystalloids for blood loss replacement. Owing to the impaired endothelial barrier, colloids leak into the interstitium. This results in an enhanced fluid shift into the interstitium. The ensuing equalized hydrostatic and oncotic pressures between the endovascular room and the interstitium and longer retention of these highmolecular-weight particles promote longer duration of interstitial edema [8]. Moreover, the use of colloids is more questionable today than ever because of their deleterious effects on coagulation and potential to induce acute renal failure. A well-considered and balanced crystalloid administration avoiding hypervolemia should be recommended [22].
3. Norepinephrine and microcirculation Counteracting the decreased sympathetic tone and the resulting hypotension, due not only to the epidural blockade
P.Y. Wuethrich, F.C. Burkhard / Urologic Oncology: Seminars and Original Investigations 33 (2015) 66.e21–66.e24
Fig. 2. Norepinephrine counteracts the vasodilation owing to anesthesia and enables maintenance of sufficient blood pressure during restrictive fluid administration. (Color version of figure is available online.)
but also to the administered anesthetics and analgesics with vasopressor (α-agonist) such as norepinephrine (Fig. 2) instead of traditional conservative fluid administration, is a rational approach. A concern associated with the preemptive use of norepinephrine is the potential impairment of microcirculation. The use of norepinephrine to counteract hypotension during restrictive fluid management for major surgery had no influence on the regional hepatosplanchnic blood flow and did not affect oxygen tension in intestinal tissue in a major surgery animal model (pigs) [23]. Hiltebrand et al. concluded that mild hypotension during a restrictive fluid management could be treated with a continuous norepinephrine administration without compromising the intestinal oxygenation. This observation is important because it indicates that tissue perfusion is warranted when a restrictive fluid management combined with the concomitant infusion of norepinephrine to maintain an adequate blood pressure is applied. In addition, continuous norepinephrine administration in dosage of 0.4 mg/kg/min increased renal blood flow and urinary output and increased coronary blood flow without any changes in mesenteric blood flow in a sheep model [24]. The administration of norepinephrine aiming to achieve a mean arterial pressure of Z65 mm Hg during septic shock resulted in an improvement of muscle tissue oxygenation and suggests that restoring arterial pressure with norepinephrine actually improves rather than worsens microcirculation in patients with severe hypotensive septic shock [25]. 4. GDT vs. restrictive fluid management GDT-guided fluid management has been reported to reduce complication rates and hospitalization time
66.e23
compared with generous fluid overload in various RCTs, including trials on radical cystectomy and urinary diversion, mostly because of shorter gastrointestinal recovery time in the GDT group [3,4,26]. The interpretation of these results is that GDT-guided fluid overload seems to be superior to liberal uncontrolled fluid overload. However, cardiac filling pressures can be poor predictors of the volume status and a low cardiac output is not automatically associated with hypovolemia [27,28]. Lobo et al. [29] showed that a restrictive fluid regimen with optimization of stroke volume and oxygen delivery index using GDT reduced the incidence of major postoperative complications in highly comorbid patients. In a multicenter trial, optimization or maximization of stroke volume, however, was not superior to a restrictive fluid management aiming for a zero postoperative weight gain in patients undergoing colorectal surgery [1]. Moreover, Challand et al. could not show any benefit of an intraoperative stroke volume optimization over standard fluid therapy during colorectal surgery in a further RCT. In a cardiopulmonary fit subgroup of patients, GDT was associated with a longer hospitalization time. This was explained by the supplemental colloid administration in the intervention group illustrating the limitations (risk of iatrogenic fluid overload) of GDT [30]. In this context, it is not surprising that Holte and Kehlet [31] recommend, in a systematic review including 80 RCTs, to avoid fluid overload in patients undergoing major surgery when applying enhanced-recovery-after-surgery protocols. In summary, a restrictive fluid management aiming at a zero postoperative weight gain should be considered the more physiological approach in major abdominal surgery. This approach will avoid or diminish the perioperative fluid shift and positively influence postoperative outcome. To achieve this goal, fluid preloading of the neuroaxial blockade should be forsaken and preemptive use of a vasopressor to correct hypotension should be applied. This presupposes accepting that evaporation from the surgical situs and pathological fluid accumulation in the surgical wound are insubstantial in elective surgery and acceptance of a low urinary output during anesthesia.
5. Conclusions The combination of norepinephrine and a restrictive fluid administration aiming for a postoperative zero fluid balance, resulting in zero weight gain on postoperative day 1, seems to be a more physiological approach in fluid management. Application of this regimen ultimately reduces the complication rate and hospitalization time and should be recommended in major urological surgery. References [1] Brandstrup B, Svendsen PE, Rasmussen M, et al. Which goal for fluid therapy during colorectal surgery is followed by the best outcome:
66.e24
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12] [13]
[14]
[15]
P.Y. Wuethrich, F.C. Burkhard / Urologic Oncology: Seminars and Original Investigations 33 (2015) 66.e21–66.e24
near-maximal stroke volume or zero fluid balance? Br J Anaesth 2012;109:191–9. Brandstrup B, Tonnesen H, Beier-Holgersen R, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens. Ann Surg 2003;238:641. Futier E, Constantin JM, Petit A, et al. Conservative vs restrictive individualized goal-directed fluid replacement strategy in major abdominal surgery: a prospective randomized trial. Arch Surg 2010;145:1193–200. Gan TJ, Soppitt A, Maroof M, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 2002;97:820–6. Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S, Matot I. Effect of intraoperative fluid management on outcome after intraabdominal surgery. Anesthesiology 2005;103:25–32. Walsh SR, Tang TY, Farooq N, Coveney EC, Gaunt ME. Perioperative fluid restriction reduces complications after major gastrointestinal surgery. Surgery 2008;143:466–8. Wuethrich PY, Burkhard FC, Thalmann GN, Stueber F, Studer UE. Restrictive deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy reduces postoperative complications and hospitalization time: a randomized clinical trial. Anesthesiology 2014;120:365–77. Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational approach to perioperative fluid management. Anesthesiology 2008;109:723–40. Wuethrich PY, Studer UE, Thalmann GN, Burkhard FC. Intraoperative continuous norepinephrine infusion combined with restrictive deferred hydration significantly reduces the need for blood transfusion in patients undergoing open radical cystectomy: results of a prospective randomised trial. Eur Urol 2014;66:352–60. Linder BJ, Frank I, Cheville JC, et al. The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol 2013;63:839–45. Morgan TM, Barocas DA, Chang SS, et al. The relationship between perioperative blood transfusion and overall mortality in patients undergoing radical cystectomy for bladder cancer. Urol Oncol 2013;31:871–7. Reithner L, Johansson H, Strouth L. Insensible perspiration during anaesthesia and surgery. Acta Anaesthesiol Scand 1980;24:362–6. Brandstrup B, Svensen C, Engquist A. Hemorrhage and operation cause a contraction of the extracellular space needing replacement— evidence and implications? A systematic review. Surgery 2006; 139:419–32. Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet 2002;359:1812–8. Jackson R, Reid JA, Thorburn J. Volume preloading is not essential to prevent spinal-induced hypotension at caesarean section. Br J Anaesth 1995;75:262–5.
[16] Matot I, Dery E, Bulgov Y, Cohen B, Paz J, Nesher N. Fluid management during video-assisted thoracoscopic surgery for lung resection: a randomized, controlled trial of effects on urinary output and postoperative renal function. J Thorac Cardiovasc Surg 2013;146:461–6. [17] Norberg A, Hahn RG, Li H, et al. Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers. Anesthesiology 2007;107:24–32. [18] Shaw AD, Bagshaw SM, Goldstein SL, et al. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 2012;255:821–9. [19] Hahn RG. Volume kinetics for infusion fluids. Anesthesiology 2010;113:470–81. [20] Riddez L, Hahn RG, Brismar B, Strandberg A, Svensen C, Hedenstierna G. Central and regional hemodynamics during acute hypovolemia and volume substitution in volunteers. Crit Care Med 1997;25:635–40. [21] Hahn RG. Fluid therapy in uncontrolled hemorrhage—what experimental models have taught us. Acta Anaesthesiol Scand 2013;57:16–28. [22] Kind SL, Spahn-Nett GH, Emmert MY, et al. Is dilutional coagulopathy induced by different colloids reversible by replacement of fibrinogen and factor XIII concentrates? Anesth Analg 2013;117:1063–71. [23] Hiltebrand LB, Koepfli E, Kimberger O, Sigurdsson GH, Brandt S. Hypotension during fluid-restricted abdominal surgery: effects of norepinephrine treatment on regional and microcirculatory blood flow in the intestinal tract. Anesthesiology 2011;114:557–64. [24] Di Giantomasso D, Morimatsu H, May CN, Bellomo R. Increasing renal blood flow: low-dose dopamine or medium-dose norepinephrine. Chest 2004;125:2260–7. [25] Georger JF, Hamzaoui O, Chaari A, Maizel J, Richard C, Teboul JL. Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients. Intensive Care Med 2010;36:1882–9. [26] Pillai P, McEleavy I, Gaughan M, et al. A double-blind randomized controlled clinical trial to assess the effect of Doppler optimized intraoperative fluid management on outcome following radical cystectomy. J Urol 2011;186:2201–6. [27] Solus-Biguenet H, Fleyfel M, Tavernier B, et al. Non-invasive prediction of fluid responsiveness during major hepatic surgery. Br J Anaesth 2006;97:808–16. [28] Jacob M, Chappell D, Rehm M. Clinical update: perioperative fluid management. Lancet 2007;369:1984–6. [29] Lobo SM, Ronchi LS, Oliveira NE, et al. Restrictive strategy of intraoperative fluid maintenance during optimization of oxygen delivery decreases major complications after high-risk surgery. Crit Care 2011;15:R226. [30] Challand C, Struthers R, Sneyd JR, et al. Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery. Br J Anaesth 2012;108:53–62. [31] Holte K, Kehlet H. Fluid therapy and surgical outcomes in elective surgery: a need for reassessment in fast-track surgery. J Am Coll Surg 2006;202:971–89.
Original article
Improved perioperative outcome with norepinephrine and a restrictive fluid administration during open radical cystectomy and urinary diversion Patrick Y. Wuethrich, M.D.a,*, Fiona C. Burkhard, M.D.b a
Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, Bern, Switzerland b Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland Received 31 March 2014; received in revised form 22 July 2014; accepted 28 July 2014
Keywords: Postoperative outcome; Radical cystectomy; Fluid therapy; Norepinephrine
Intravenous fluid administration is fundamental in the perioperative period to replace the fluid lost during major surgery and to maintain physiological organ function. The optimal intraoperative fluid volume to be administered, however, is a matter of intense debate, and controversy persists in terms of how much fluid has to be infused, choice of fluids (crystalloids or colloids), concomitant administration of vasopressors, or a goal-directed hemodynamic therapy (GDT) aiming for an optimization or maximization of the stroke volume [1–6]. Intravenous fluids should be considered as drugs and consequently indication, timing, and dosage are relevant, regardless of the type of fluid. 1. Norepinephrine and restrictive fluid management: Less postoperative complications In 2 recent publications from a randomized clinical trial (RCT), we analyzed the impact of 2 different fluid managements on the postoperative complication rate (primary end point), intraoperative blood loss, and the packed red blood cell (PRBC) transfusion rate (secondary end points) in patients undergoing open radical cystectomy with urinary diversion. One group (norepinephrine/low volume) received a continuous norepinephrine infusion starting during the induction of anesthesia at a rate of 2 mg/kg/h combined with a restrictive deferred fluid administration (1 ml/kg/h until the bladder was removed and then 3 ml/kg/h until the end of surgery). Hypotension was corrected by adapting the norepinephrine infusion rate. This approach resulted in a Corresponding author. Tel.: þ413-1-632-2725; fax: þ416-3-205-54. E-mail address: [email protected] (P.Y. Wuethrich). *
http://dx.doi.org/10.1016/j.urolonc.2014.07.018 1078-1439/r 2014 Elsevier Inc. All rights reserved.
median crystalloid administration of 1,700 ml (range: 700– 4,000) and a median norepinephrine infusion rate of 3.6 mg/ kg/h (2.0–8.0). The other group (control) received a constant infusion rate of 6 ml/kg/h throughout surgery without norepinephrine administration. Hypotension was corrected by administering fluid boluses. This resulted in a median crystalloid administration of 4,300 ml (2,800–6,200). The overall in-hospital complication rate was significantly reduced in the norepinephrine/low-volume group (52% vs. 73%), and there was an almost a 50% reduction in the 90-day postoperative major complication rate grades III to V, according to the Clavien Dindo classification (13% vs. 25%) [7]. In our study, a zero postoperative weight gain was observed in the norepinephrine/low-volume group (Fig. 1). Postoperative body weight gain is a reliable marker of fluid overload with extravascular fluid accumulation (edema) and correlates with an increased postoperative complication and mortality rates [2,8]. This strongly suggests minimal or no clinically relevant interstitial edema formation in the norepinephrine/low-volume group with an ensuing faster return of bowel function and a reduced rate of gastrointestinal complications in this group (6% vs. 37%). Ultimately, as a consequence of the lower complication rate, the hospitalization time was significantly reduced by 2 days in the norepinephrine/low-volume group [7]. Intraoperative blood loss was decreased in the norepinephrine/low-volume group (800 vs. 1,200 ml), and interestingly the PRBC transfusion rate was reduced not only intraoperatively (8% vs. 33%) but also throughout the hospitalization (33% vs. 60%) [9]. As the number of PRBCs given may have a significant negative effect on cancer-related outcomes and overall survival in patients undergoing radical cystectomy for bladder cancer [10,11], this fact is not to be neglected.
66.e22 3
P.Y. Wuethrich, F.C. Burkhard / Urologic Oncology: Seminars and Original Investigations 33 (2015) 66.e21–66.e24 *
*
Body Weight Changes
2 1 0 -1 -2 -3
POD 1
POD2
POD3
POD4
POD5
Discharge
Fig. 1. Postoperative weight-gain (kg) differences presented as the mean with 95% CIs after radical cystectomy and urinary diversion in the 2 groups (yellow: norepinephrine/low-volume group [n ¼ 83] and purple: control group [n ¼ 83] with liberal fluid administration) (*P o 0.05, POD ¼ postoperative day). (Color version of figure is available online.)
2. Perioperative restrictive fluid management is the more physiological fluid approach Standard perioperative fluid management aims to replace basal fluid requirements, perspiration/exudation through the surgical situs, loss to the third space, blood loss, and preloading of the neuroaxial blockade. This traditional approach to fluid substitution management inevitably causes a postoperative positive fluid balance illustrated by a body weight gain on postoperative day 1. The primary explanation for this fluid overload is an overestimation of the fluid required to replace loss into the third space and through the surgical wound, which is lower than generally assumed. Insensible perspiration is around 0.5 ml/kg/h in the normal condition and increases to a maximum of 1 ml/kg/h intraoperatively [12]. The loss into the third space is questionable and most likely does not exist [13]. Fluid volume substitution according to textbook recommendations of 10 to 15 ml/kg/h for major intra-abdominal surgery is not evidence based and is increasingly being challenged [1,2,14]. In a multicenter RCT evaluating a restrictive fluid management during colorectal surgery, a zero weight gain postoperatively resulted in a faster return of gastrointestinal function, reduced postoperative complications, and a shorter hospitalization. In addition, fluid overload was shown to decrease pulmonary function and lead to pulmonary edema [2,14]. A further study showed that preemptive preloading fluid administration during neuroaxial blockade is not effective, as it does not prevent anesthesia-related hypotension [15] and inevitably results in fluid overload and postoperative weight gain. Another issue is the idea that a generous intraoperative fluid administration maintains systemic blood pressure and protects organ function, especially renal function. However, liberal fluid administration has not been shown to decrease the incidence of acute renal failure. Basically, urinary output is reduced perioperatively as a result of a stress reaction with activation of the antidiuretic hormone, aldosterone, and the renin-angiotensin II system. Increased antidiuretic hormone
secretion enhances renal water reabsorption and increased secretion of aldosterone and renin leads to conservation of sodium and excretion of potassium. Consequently, patients have a decreased urinary output and a tendency to retain fluid because administered fluids are not readily excreted, thus contributing to a postoperative fluid overload. Matot et al. [16] could demonstrate that urinary output was not affected by doubling the amount of fluid administered during thoracoscopic surgery. Intraoperative administration of α-1 and β-1 mimetics, which influence the reninangiotensin-aldosterone and the adrenergic systems, could enhance urinary output and would be beneficial [17]. Physiological, balanced crystalloid solutions (Ringer's lactate or Ringer's maleate as administered in our RCT) should be used instead of a 0.9% sodium chloride solution. Hyperchloremia and hyperchloremic metabolic acidosis can be caused by fluid resuscitation with 0.9% sodium chloride solution and consequently renal blood flow will be reduced. In addition, the administration of a balanced crystalloid solution perioperatively decreased the rate of postoperative infections, renal replacement therapy, blood transfusion, and acidosis-associated investigations compared with a 0.9% saline solution for major abdominal surgery in an observational study [18]. The need for replacement of intraoperative blood loss is evident. However, volume effects are context sensitive and different during anesthesia and surgery, as renal clearance of crystalloid fluid is only 15% to 20% of that found in healthy nonanesthetized volunteers [19]. Conventional colloid (1:1) or crystalloid (3:1) administration in proportion to the amount of blood loss can cause transient hypervolemia and promote serious rebleeding [20,21]. Acute hypervolemia can alter or destroy the endothelial surface layer (glycocalyx), which is the key structure of the vascular barrier. Transient hypervolemia due to fluid overload can induce a relevant fluid and protein shift toward the interstitium, resulting in interstitial edema with the ensuing negative effects on bowel function. Colloids are not superior to crystalloids for blood loss replacement. Owing to the impaired endothelial barrier, colloids leak into the interstitium. This results in an enhanced fluid shift into the interstitium. The ensuing equalized hydrostatic and oncotic pressures between the endovascular room and the interstitium and longer retention of these highmolecular-weight particles promote longer duration of interstitial edema [8]. Moreover, the use of colloids is more questionable today than ever because of their deleterious effects on coagulation and potential to induce acute renal failure. A well-considered and balanced crystalloid administration avoiding hypervolemia should be recommended [22].
3. Norepinephrine and microcirculation Counteracting the decreased sympathetic tone and the resulting hypotension, due not only to the epidural blockade
P.Y. Wuethrich, F.C. Burkhard / Urologic Oncology: Seminars and Original Investigations 33 (2015) 66.e21–66.e24
Fig. 2. Norepinephrine counteracts the vasodilation owing to anesthesia and enables maintenance of sufficient blood pressure during restrictive fluid administration. (Color version of figure is available online.)
but also to the administered anesthetics and analgesics with vasopressor (α-agonist) such as norepinephrine (Fig. 2) instead of traditional conservative fluid administration, is a rational approach. A concern associated with the preemptive use of norepinephrine is the potential impairment of microcirculation. The use of norepinephrine to counteract hypotension during restrictive fluid management for major surgery had no influence on the regional hepatosplanchnic blood flow and did not affect oxygen tension in intestinal tissue in a major surgery animal model (pigs) [23]. Hiltebrand et al. concluded that mild hypotension during a restrictive fluid management could be treated with a continuous norepinephrine administration without compromising the intestinal oxygenation. This observation is important because it indicates that tissue perfusion is warranted when a restrictive fluid management combined with the concomitant infusion of norepinephrine to maintain an adequate blood pressure is applied. In addition, continuous norepinephrine administration in dosage of 0.4 mg/kg/min increased renal blood flow and urinary output and increased coronary blood flow without any changes in mesenteric blood flow in a sheep model [24]. The administration of norepinephrine aiming to achieve a mean arterial pressure of Z65 mm Hg during septic shock resulted in an improvement of muscle tissue oxygenation and suggests that restoring arterial pressure with norepinephrine actually improves rather than worsens microcirculation in patients with severe hypotensive septic shock [25]. 4. GDT vs. restrictive fluid management GDT-guided fluid management has been reported to reduce complication rates and hospitalization time
66.e23
compared with generous fluid overload in various RCTs, including trials on radical cystectomy and urinary diversion, mostly because of shorter gastrointestinal recovery time in the GDT group [3,4,26]. The interpretation of these results is that GDT-guided fluid overload seems to be superior to liberal uncontrolled fluid overload. However, cardiac filling pressures can be poor predictors of the volume status and a low cardiac output is not automatically associated with hypovolemia [27,28]. Lobo et al. [29] showed that a restrictive fluid regimen with optimization of stroke volume and oxygen delivery index using GDT reduced the incidence of major postoperative complications in highly comorbid patients. In a multicenter trial, optimization or maximization of stroke volume, however, was not superior to a restrictive fluid management aiming for a zero postoperative weight gain in patients undergoing colorectal surgery [1]. Moreover, Challand et al. could not show any benefit of an intraoperative stroke volume optimization over standard fluid therapy during colorectal surgery in a further RCT. In a cardiopulmonary fit subgroup of patients, GDT was associated with a longer hospitalization time. This was explained by the supplemental colloid administration in the intervention group illustrating the limitations (risk of iatrogenic fluid overload) of GDT [30]. In this context, it is not surprising that Holte and Kehlet [31] recommend, in a systematic review including 80 RCTs, to avoid fluid overload in patients undergoing major surgery when applying enhanced-recovery-after-surgery protocols. In summary, a restrictive fluid management aiming at a zero postoperative weight gain should be considered the more physiological approach in major abdominal surgery. This approach will avoid or diminish the perioperative fluid shift and positively influence postoperative outcome. To achieve this goal, fluid preloading of the neuroaxial blockade should be forsaken and preemptive use of a vasopressor to correct hypotension should be applied. This presupposes accepting that evaporation from the surgical situs and pathological fluid accumulation in the surgical wound are insubstantial in elective surgery and acceptance of a low urinary output during anesthesia.
5. Conclusions The combination of norepinephrine and a restrictive fluid administration aiming for a postoperative zero fluid balance, resulting in zero weight gain on postoperative day 1, seems to be a more physiological approach in fluid management. Application of this regimen ultimately reduces the complication rate and hospitalization time and should be recommended in major urological surgery. References [1] Brandstrup B, Svendsen PE, Rasmussen M, et al. Which goal for fluid therapy during colorectal surgery is followed by the best outcome:
66.e24
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12] [13]
[14]
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P.Y. Wuethrich, F.C. Burkhard / Urologic Oncology: Seminars and Original Investigations 33 (2015) 66.e21–66.e24
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