Fluids in the PACU: The Impact on Acute Kidney Injury
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1) Fluid overload is associated with worse outcomes in patients with acute kidney injury (AKI), including increased mortality and decreased renal recovery. Several studies have shown relationships between greater fluid accumulation and higher risk of death. 2) Fluid balance may also impact renal recovery - more positive fluid balances are linked to less renal recovery in some studies. Restricting fluids appears beneficial for outcomes in some patients. 3) Choice of IV fluid may also influence AKI risk. Hydroxyethyl starches (HES) and liberal albumin administration are associated with higher rates of AKI compared to crystalloids in some studies. Chloride-restrictive IV solutions may reduce AKI compared to chloride-liberal fluids.
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Fluids in the PACU: The Impact on Acute Kidney Injury
- 1. Fluids in the PACU, the easy way out? Max Bell MD, PhD Karolinska University Hospital/Karolinska Institutet
- 2. Importance Acute kidney injury (AKI) is common after surgery It is associated with increased mortality and long-term renal dysfunction Perhaps there is room for improvement, preoperatively, intraoperatively and in the postoperative period
- 3. How common? Curr Opin Crit Care. 2017 Aug 17
- 4. How dangerous? •“At 10-year follow-up, adjusted cardiovascular-specific mortality estimates were 6%, 11%, 12%, 19%, and 27% for patients with no kidney disease, AKI with no CKD, CKD with no AKI, AKI with CKD, and ESRD, respectively (P < 0.001).” •Registry study (single center) of >50 000 patients Ann Surg. 2016 Dec;264(6):987-996. •”In eight studies that reported the short-term mortality, relative risk of death in the presence of post-operative AKI was 12.6 fold (95% CI, 6.8-23.4).” •Systematic review (in total n=82,514; 19 studies) Intensive care medicine. 2016;42(4):521-30.
- 5. Pathophysiology (major surgery->AKI), simplified •Major surgery involves large shifts in volume •Hypotension is common (and perhaps underappreciated*) •Blood loss •Intraperitoneal insults can compromise renal blood flow •Inflammation-surgical trauma •Other adverse events like massive blood loss-transfusion, severe hypotension, bacterial leakage, hypoxia etc
- 6. Pathophysiology (major surgery->AKI), simplified (2) •Use of harmful substances for the kidney such as contrast media, nephrotoxic antibiotics, and NSAIDs •Preop: •Advanced age •Comorbidities (common+predispose to a greater risk of AKI) •Diabetes •Chronic kidney disease (CKD) •Heart failure •Demographic shifts: complex surgery is now performed in older and more chronically ill patients, increasing the number of patients at risk
- 7. Pathophysiology (fluid overload->AKI) CI >3.2 CI 2.5-3.2 CI <2.5
- 9. Prevention of postoperative AKI [preop] •Identify patients at risk •Advanced age •CKD •Multiple comorbidities •Surgery during critical illness •Surgery with an ongoing infection •Planned surgery will compromise renal blood flow? •Act •Surgical approach in high risk patients (no data but endovascular aortic repair>open AAA surgery with renal flow occlusion?) •Correct anemia
- 10. Prevention of postoperative AKI [intraop] •Identify patients at risk •Advanced age •CKD •Multiple comorbidities •Surgery during critical illness •Surgery with an ongoing infection •Planned surgery will compromise renal blood flow? •Act •Extreme vigilance with regards to hypotension – use patients own baseline* •Avoid hypovolemia •Adequate (so, so easy to write) cardiac output •Avoid (if possible) starch, contrast, aminoglycosides, NSAIDs •Beware of hypervolemia! •Transfusions when necessary •Intraoperative oliguria – not always a trigger for volume! •Diuretics in hypervolemia *if* positive response
- 11. *Hypotension and AKI • Univariate analysis – Sex – Comorbity – BP medication – Preop creatinine – Intraop hypotension – Postop fluid balance EJA 2017, In Press
- 12. *Hypotension and AKI Risk factor OR (unadjusted) (95% CI) OR (adjusteda) (95% CI) OR (adjustedb) (95% CI) Hypotensive event* (>40-≤50%) vs ≤40% 1.56 (0.98- 2.48) 1.61 (0.99-2.62) 1.48 (0.90-2.44) Hypotensive event* (>50%) vs ≤ 40% 2.38 (1.30- 4.36) 2.27 (1.20-4.30) 2.02 (1.05-3.89) EJA 2017, In Press *Decrease in systolic blood pressure in percent relative to baseline for >5 min. aAdjusted for the covariates: gender (male), ASA>2, treated hypertension, pre-operative creatinine >90µmol/L and fluid balance in quartiles. b Adjusted for the covariates mentioned above and blood loss in quartiles. •Multivariable analysis
- 13. Goal directed prevention of postoperative AKI [intraop] •The OPTIMISE trial (major GI surgery) found a cardiac output-guided fluid and vasopressor treatment algorithm to lead to fewer postoperative complications (such as ischemic insults, respiratory failure, and AKI), but no postop mortality reduction JAMA 2014; 311: 2181–2190 •RCT of transpulmonary thermodilution to guide goal-directed therapy neither found the intervention to increase the rate of achieved hemodynamic targets (!) nor (unsurprisingly) to reduce the postoperative increase in creatinine •But same study - intraoperative hypotension and hypovolemia: the most important risk factors for postoperative AKI Crit Care 2016; 20:50
- 14. Fluids peri- and postoperatively •OPTIMISE: total amount of iv fluids did not differ between the treatment arms, ~4000 ml, but the intervention group received more colloids of any type….even starch… •Ok, so avoid starch (6S, CHEST etc) •Balanced solutions>0.9% sodium chloride? (SPLIT trial, but more data needed) •RELIEF: restrictive vs liberal fluid therapy in major abdominal surgery •Randomized 3000 patients and one endpoint is AKI assessed by creatinine [to be published in 2018] •Peri/postoperative oliguria – a trigger for fluids? Sometimes yes, more often nope, nein, nichts, nihil, nej. Goren O, Matot I. Perioperative acute kidney injury. Br J Anaesth 2015; 115(Suppl 2):ii3–ii14
- 15. More on fluids in the PACU •A meta-analysis including RCTs comparing goal-directed therapy with standard therapy in mixed patient populations found GDT to prevent AKI – but…. •Wide periods of time – large shifts in how we use fluids, both with regards to overall volume and type of fluid Anesth Analg 2016; 122:173–185. •The use of “maintenance fluids” in AUS/NZ has decreased significantly from 2011-14 Crit Care Resusc 2016; 18:89–94 •Use of starch for obv reasons in decline; 67% reduction in AUS/NZ and 82% in Denmark Acta Anaesthesiol Scand 2017; 61:532–538. Crit Care Resusc 2017; 19:134–141.
- 16. Fluids in the PACU: conclusions •Varying definitions for AKI have distorted comparability of studies •Around one-fifth of patients undergoing major noncardiac surgery develop an increase in creatinine or oliguria or both •AKI increases risk for postop adverse outcomes including death •Recognizing high-risk patients preoperatively: important! •Prompt treatment of intraoperative hypotension and hypoperfusion •Avoiding nephrotoxins •The large multicenter RCT of restrictive vs liberal fluid management in major abdominal surgery (RELIEF) will aid in how to optimize perioperative fluid management
- 17. Early Goal-Directed Therapy (EGDT) Rivers et al, NEJM 2001
- 18. Fluid balance vs mortality in AKI patients
- 19. American Journal of Kidney Diseases Volume 55, Issue 2, February 2010, Pages 316–3
- 20. American Journal of Kidney Diseases Volume 55, Issue 2, February 2010, Pages 316–325
- 21. Fluid accumulation and 60-day mortality data from the SOAP study Payen et al, Critical Care 2008
- 22. Fluid overload and 60-day mortality a PICARD study Bouchard et al, Kidney Int 2009 Adjusted OR* 95% CI FO at dialysis initiation 2.07 1.27–3.37 FO at dialysis cessation 2.52 1.55–4.08 FO at AKI diagnosis (non-dialyzed patients) 3.14 1.18–8.33 *Adjusted for illness severity (APACHE III score) and initial dialysis modality Adjusted OR for death associated with fluid overload (FO) FO: Fluid-related weight gain of >10% over baseline (Total fluid intake – Total output) × 100 / body weight
- 23. Fluid balance and 60-day mortality in AKI patients with ALI data from the FACTT Grams et al, Clin J Am Soc Nephrol 2012
- 24. Fluid balance and 60-day mortality in AKI patients with ALI data from the FACTT Grams et al, Clin J Am Soc Nephrol 2012 Adjusted OR* 95% CI P Fluid Balance post-AKI (mean L/day) 1.61 1.32-1.96 <0.001 * Adjusting for age, sex, race, fluid-strategy randomization group, catheter randomization group, day first diagnosed with AKI, APACHE III score, mean daily CVP, presence of shock
- 25. Fluid balance and 28-day mortality in AKI patients data from the NEFROINT study Teixeira et al, Critical Care 2013
- 26. Fluid balance and 28-day mortality in AKI patients data from the NEFROINT study Teixeira et al, Critical Care 2013 Adjusted HR* 95% CI P Mean Fluid Balance (L/day) 1.67 1.33-2.09 <0.001 Mean Urine Volume (L/day) 0.47 0.33-0.67 <0.001 Diuretic use 0.25 0.12-0.52 <0.001 Diabetes 2.16 1.09-4.26 0.027 Hypertension 2.18 1.12-4.22 0.021 * Variables considered in the model: age, gender, diabetes, hypertension, cardiovascular disease, non-renal SOFA, sepsis, mean fluid balance, mean urine volume and diuretic use Table 3. Cox regression analysis for 28-day mortality
- 27. Fluid overload at RRT initiation and 90-day mortality data from the FINNAKI study Vaara et al, Critical Care 2012
- 28. Fluid overload at RRT initiation and 1-year mortality Heung et al, Nephrol Dial Transplant 2012
- 29. Fluid balance vs mortality during RRT
- 30. Intensity of CRRT and 90-day mortality the RENAL Study Investigators, N Engl J Med 2009
- 31. Fluid balance during CRRT and 90-day mortality post-hoc from the RENAL study the RENAL Study Investigators, Crit Care Med 2012 Survival
- 32. Fluid overload and 60-day mortality a PICARD study Bouchard et al, Kidney Int 2009
- 33. Does fluid balance have an impact on renal recovery?
- 34. Fluid balance and renal recovery Reference Study type Population (n) Mean fluid balance in restrictive group Mean fluid balance in liberal group Renal outcome with more restrictive strategy FACTT, 2006 RCT ALI (1,000) -136 ml on day 7 +6,992 ml on day 7 Trend toward less RRT (p = 0.06) Bouchard, 2009 Retrospective Mixed ICU+AKI (542) <10% rise at AKI diagnosis or RRT initiation >10% rise at AKI diagnosis or RRT initiation No difference Bouchard, 2009 Retrospective Mixed ICU+AKI (542) <10% rise at peak creatinine >10% rise at peak creatinine Increased renal recovery (p = 0.007, adjusted for APACHE III score) Grams, 2011 (FACTT) Retrospective ALI and AKI (306) +3,700 ml on day 7 +10,200 ml on day 7 No difference in RRT requirement Heung, 2012 Retrospective RRT (170) <10% fluid overload at RRT initiation >10% fluid overload at RRT initiation Increased likelihood of RRT discontinuation within 1 year (p = 0.02) RENAL, 2012 Retrospective RRT (1,453) Negative mean daily FB Positive mean daily FB Increased RRT-free days (p = 0.0017)
- 35. Increased renal vein pressure and kidney failure Firth et al, Lancet 1988
- 36. Association between CVP and renal function Damman et al, JACC 2009 CVP (mmHg) CI >3.2 CI 2.5-3.2 CI <2.5
- 37. Choice of fluid
- 38. Fluids HES vs. crystalloids Reference Study type Patients (n) Fluids Outcome with HES VISEP trial, 2008 RCT Severe sepsis (537) 10% HES 200/0.5 vs. Ringer’s lactate More AKI (p = 0.002) More RRT (p = 0.001) Schortgen, 2008 Prospective cohort study Shock (822) Increased risk for AKI with artificial hyperoncotic colloids (OR 2.13) Rioux, 2009 Retrospective Cardiac surgery (563) HES 200/0.5 vs. Pentastarch associated with an increased risk of AKI (OR 1.08 per ml/kg) Perner, 2012 (6S) RCT Severe sepsis (804) 6% HES 130/0.4 vs. Ringer-Acetate Myburgh, 2012 (CHEST) RCT ICU (7000) 6% HES 130/0.4 vs. 0.9% Saline More patients needed RRT (RR 1.21 [1.00-1.45]). No difference in 90-day mortality
- 39. Fluids Albumin vs. Crystalloids Reference Study type Patients (n) Fluids Outcome with Albumin Schortgen, 2008 Prospective cohort study Shock (232) 20-25% Albumin vs. Crystalloids Increased risk for AKI (OR 5.27 [2.44-11.37]) and ICU mortality (OR 2.76 [1.41-5.41]) SAFE study, 2004 RCT ICU (7000) 4% Albumin vs. 0.9% saline No difference in duration of RRT or 28-day mortality SAFE substudy on TBI, 2007 Post hoc TBI (406) 4% Albumin vs. 0.9% saline Higher 2-year mortaity (OR 1.63 [1.17-2.26]) SAFE substudy on severe sepsis, 2011 Post hoc Severe sepsis (1218) 4% Albumin vs. 0.9% saline Lower 2-year mortality (OR 0.7 [0.52-0.97]) No difference in renal SOFA or RRT requirement
- 40. Fluids Chloride liberal vs. Chloride restrictive Reference Study type Patients (n) Fluids Outcome with Chloride- restrictive strategy Yunos, 2012 Prospective cohort study ICU (1533) Liberal administration of chloride-rich solutions vs. Chloride restrictive strategy Decreased risk for AKI (OR 0.52 [0.37-0.75]) and use of RRT (OR 0.52[0.33-0.81]) Shaw, 2012 Retrospective cohort study Surgery (3704) 0.9% Saline vs. Plasma-Lyte® Less need for acute dialysis (p <0.001)
- 41. Over-zealous fluid resuscitation may lead to fluid overload. Can fluid overload worsen AKI? • Link between FO, abdominal compartment syndrome and AKI (Dalfino, 2008 707-713) • Elevated CVP strong predictor of progression of renal failure in CHF patients (Mullens, 2009 598-596) • AKI is associated with elevated renal interstitial pressure (reflecting renal edema) (Herrler, 2010 40-46) Summary
- 43. Prompt and targeted correction of volume deficit – may reduce later volume requirements. Stop when preload is sufficient to generate adequate CO – may require earlier or greater use ov vasopressors Recommendations
Editor's Notes
- Use of fluids and fluid overload: extremely difficult to draw conclusions from non-randomized trials
- A large retrospective analysis in 2557 patient from our center that underwent right heart catheterization showed that central venous pressure (CVP) is associated with estimated GFR (eGFR) in a bimodal fashion, with the highest eGFR at a CVP of approximately 3 mmHg and a progressively lower eGFR in subjects with CVP above 5–6 mm Hg, comprising approximately one-third of the population. Remarkably, is shown in Fig. 1 , this bimodal association was independent of cardiac index (the analysis was adjusted for age, sex and cardiac index) The right figure shows the association between CVP and GFR according to different cardiac index values
- A six-hour initial resuscitation bundle, including aggressive fluid administration was associated with better prognosis (Rivers, 2001). In that trial, fluid administration was greater in the treatment group from 0 to 6 h, but, importantly, overall fluid administration was not significantly different between groups over the first 72 h These data suggest that prompt, targeted resuscitation can spare later fluid requirements.
- Vätskeöverskott vid CRRT-start hos kritiskt sjuka barn – data från the prospective pediatric CRRT registry (ppCRRT). %VÄTSKEÖVERSKOTT= Vätska in-vätska ut/IVA-in-vikt *100%. American Journal of Kidney Diseases Volume 55, Issue 2, February 2010, Pages 316–325 Original Investigation Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry Scott M. Sutherland, MD1, , , Michael Zappitelli, MD, MSc2, Steven R. Alexander, MD1, Annabelle N. Chua, MD3, Patrick D. Brophy, MD4, Timothy E. Bunchman, MD5, Richard Hackbarth, MD5, Michael J.G. Somers, MD6, Michelle Baum, MD6, Jordan M. Symons, MD7, Francisco X. Flores, MD8, Mark Benfield,MD9, David Askenazi, MD9, Deepa Chand, MD10, James D. Fortenberry, MD11, John D. Mahan, MD12, Kevin McBryde, MD13, Douglas Blowey, MD14, Stuart L. Goldstein, MD3
- 1120 pts with ARF from SOAP. In addition, multivariate regression analysis demonstrated that mean daily fluid was a significant and independent mortality predictor. Specifically, a 1 L positive fluid balance per 24 hrs was associated with an approximate 20% increase in mortality risk.
- This trial was an observational study in which fluid status was estimated quantitatively in 610 AKI patients. Of these patients, approximately two-thirds (396) required some form of dialysis. Fluid balance was estimated by measuring the sum of all fluid inputs (e.g., intravenous fluids, medications, nutrition, etc) and the sum of all fluid outputs (e.g., urine, stool, nasogastric fluid, etc). On a daily basis, “fluid accumulation” was calculated as the difference in these sums divided by the body weight at the time of hospital admission. These measurements were made starting three days before nephrology consultation and continued until hospital discharge. The study defined “fluid overload” as a fluid accumulation value of greater than 10% (i.e., the point at which a patient sustained a fluid-related weight gain of 10% from baseline). As shown in the table, the patients who met the 10% fluid overload criterion at the time of AKI diagnosis were more critically ill than patients with lesser degrees of fluid accumulation. The fluid overload group had significantly higher APACHE III and SOFA scores, higher number of organ failures, and higher percentage of patients with respiratory failure, ventilator dependence, and sepsis or septic shock. It should be noted that the outcomes reported below are adjusted for the greater illness severity in the fluid overload group.
- From the 1000 participants in FACTT, Grams and coworkers identified 306 patients meeting AKIN criteria for stage 1 AKI in the first 2 study days. These patients were included in this post-hoc analysis of the relationship between fluid balance and mortality. Fluid balance was calculated as the mean daily difference between fluid intake and fluid output from the development of AKI until day 7, death or withdrawal from study.
- Fluid balance was calculated as the mean daily difference between fluid intake and fluid output from the development of AKI until day 7, death or withdrawal from study. In a multiple logistic regression model adjusting for multiple co-variates, they found a 61% increase in the risk of death for every 1 L increase in mean fluid balance per day. This association was consistent through multiple sensitivity analyses and across gender, fluid strategy, early and late oliguria and severity of AKI.
- This secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs examined the influence of fluid balance and urine volume on 28-day mortality among critically ill patients with AKI. 132 patients with AKI (defined by renal SOFA score). This Figure demonstrates the pattern of cumulative fluid balance among survivors and non-survivors in the first 7 days in the ICU. Non-survivors consistently had higher mean cumulative fluid balance throughout the ICU stay and the magnitude of the difference between the groups increased with each additional day.
- The cox regression analysis showed that mean fluid balance was independently associated with mortality. In this analysis, for every 1 L increase in mean fluid balance per day, a 67% increase in the risk of death was observed.
- Retrospective analysis of 170 hospitalized adult patients with AKI who required RRT. Appprox. 60% received CRRT as initial modality. Most patients (80%) were treated in the ICU. %FO = (weight at RRT initiation – baseline weight) x 100/Baseline weight
- They found no difference in mortality. The RENAL trial tested high vs. low intensity CRRT in 1500 ICU patients, and found no difference in 90 day mortality.
- The same authors recently performed a post-hoc crunch of the data from the original RCT. They created separate survival plots for patients with or without a positive mean daily fluid balance during the first two study days (left fig) and from day 2 and onwards. Both analyses showed increased mortality in patients with early or late positive fluid balance. A negative mean daily fluid balance was associated with a nearly 70% reduction in 90-day risk of death. Negative fluid balance was also independently associated with increased RRT-free days and fewer ICU and hospital days (p < 0.01).
- In dialyzed patients, mortality increased in relation to the proportion of dialysis days with fluid overload. In the ICU, use of CRRT allows slow progressive fluid removal compared to the use of intermittent hemodialysis which has been associated with progressive fluid overload
- Isolated rat kidneys were perfused with a constant pressure and stepwise incrememnts in renal vein pressure were investigated. GFR and sodium excretion fell progressively with increasing venous pressure. The underlying mechanism is still unknown but interstitial edema, increased distal tubular pressure as well as effects on renal blood flow and humoral factors mays play a role,
- A large retrospective analysis in 2557 patient from our center that underwent right heart catheterization showed that central venous pressure (CVP) is associated with estimated GFR (eGFR) in a bimodal fashion, with the highest eGFR at a CVP of approximately 3 mmHg and a progressively lower eGFR in subjects with CVP above 5–6 mm Hg, comprising approximately one-third of the population. Remarkably, is shown in Fig. 1 , this bimodal association was independent of cardiac index (the analysis was adjusted for age, sex and cardiac index) The right figure shows the association between CVP and GFR according to different cardiac index values
- Fluid balance is not reported in these studies.
- Schotgen an colleagues compared the effect of hyperoncotic albumin vs. crystalloids on kidney function and ICU mortality in patients with shock. Resuscitation with hyperoncotic albumin was associated with an increased risk of AKI and mortality. The SAFE study randomized 7000 ICU patients to either 4% Albumin or normal saline for fluid resuscitation and found no differences in 28-day mortality or renal outcomes.