Abstracts
Acute kidney injury (AKI) has a high hospital incidence and is associated to significant morbidity and mortality. Sepsis, major surgery and low cardiac output are the main cause of AKI worldwide. In the majority of these situations, volume expansion is part of both prevention and therapeutic management, restoring peripheral perfusion and attenuating drug nephrotoxicity. Early and aggressive volume resuscitation in septic patients halts tissue ischemia and is associated with higher survival. However, a liberal fluid infusion strategy after six hours can cause fluid overload. Fluid overload has been associated with morbidity and mortality increase in critically ill patients. Herein, we present a review of the main studies that assessed the effects of net fluid balance/fluid overload on the morbidity and mortality of critically ill patients. We suggest that positive water balance may be used as a potential early biomarker of AKI in these patients.
acute kidney injury; intensive care unit; mortality; water balance
Injúria renal aguda (IRA) é uma síndrome de elevada incidência, associada a altas taxas de morbimortalidade. Sepse, grandes cirurgias e baixo débito cardíaco são as principais causas de IRA no mundo. Na maioria destas situações clínicas, a expansão volêmica é o elemento fundamental de prevenção e do manejo terapêutico da IRA, restaurando a perfusão periférica e atenuando a nefrotoxicidade de drogas. Ressuscitação volêmica precoce em pacientes sépticos está associada à prevenção de isquemia tecidual e à maior sobrevida. Contudo, a manutenção de estratégia liberal de infusão de fluidos após ressuscitação inicial pode causar balanços hídricos cumulativamente positivos, e este vem sendo associado a aumento de morbimortalidade em pacientes criticamente enfermos. Neste trabalho, revisamos os principais estudos que associam balanço hídrico positivo (BH+) e morbimortalidade em pacientes internados em Unidades de Terapia Intensiva (UTI). Sugerimos que BH+ (não apenas o volume urinário) possa ser utilizado como possível biomarcador precoce de IRA nestes pacientes.
balanço hídrico; insuficiência renal aguda; mortalidade; unidades de terapia intensiva
Acute kidney injury and volume expansion: is positive fluid balance (FB+) beneficial?
Acute kidney injury (AKI) happens in approximately 3% to 15% of hospitalized patients
and can affect 30% to 50% of patients allocated to intensive care units (ICU).11 Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, et al.
Continuous renal replacement therapy: a worldwide practice survey. The beginning and
ending supportive therapy for the kidney (B.E.S.T. kidney) investigators. Intensive
Care Med 2007;33:1563-70.
2 Fang Y, Ding X, Zhong Y, Zou J, Teng J, Tang Y, et al. Acute kidney
injury in a Chinese hospitalized population. Blood Purif 2010;30:120-6. DOI:
http://dx.doi.org/10.1159/000319972
http://dx.doi.org/10.1159/000319972...
3 Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk
stratification, and outcomes. Kidney Int 2012;81:819-25. PMID: 21975865 DOI:
http://dx.doi.org/10.1038/ki.2011.339
http://dx.doi.org/10.1038/ki.2011.339...
4 Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute
kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442-8. PMID:
22113526 DOI: http://dx.doi.org/10.1038/ki.2011.379
http://dx.doi.org/10.1038/ki.2011.379...
-55 Bucaloiu ID, Kirchner HL, Norfolk ER, Hartle JE 2nd, Perkins RM.
Increased risk of death and de novo chronic kidney disease following reversible acute
kidney injury. Kidney Int 2012;81:477-85. PMID: 22157656 DOI:
http://dx.doi.org/10.1038/ki.2011.405
http://dx.doi.org/10.1038/ki.2011.405...
AKI overall hospital mortality is approximately 20% and may exceed 50%
in critically ill patients.11 Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, et al.
Continuous renal replacement therapy: a worldwide practice survey. The beginning and
ending supportive therapy for the kidney (B.E.S.T. kidney) investigators. Intensive
Care Med 2007;33:1563-70.
2 Fang Y, Ding X, Zhong Y, Zou J, Teng J, Tang Y, et al. Acute kidney
injury in a Chinese hospitalized population. Blood Purif 2010;30:120-6. DOI:
http://dx.doi.org/10.1159/000319972
http://dx.doi.org/10.1159/000319972...
-33 Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk
stratification, and outcomes. Kidney Int 2012;81:819-25. PMID: 21975865 DOI:
http://dx.doi.org/10.1038/ki.2011.339
http://dx.doi.org/10.1038/ki.2011.339...
Patients who develop in-hospital AKI have
higher risk of developing chronic kidney disease,44 Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute
kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442-8. PMID:
22113526 DOI: http://dx.doi.org/10.1038/ki.2011.379
http://dx.doi.org/10.1038/ki.2011.379...
,55 Bucaloiu ID, Kirchner HL, Norfolk ER, Hartle JE 2nd, Perkins RM.
Increased risk of death and de novo chronic kidney disease following reversible acute
kidney injury. Kidney Int 2012;81:477-85. PMID: 22157656 DOI:
http://dx.doi.org/10.1038/ki.2011.405
http://dx.doi.org/10.1038/ki.2011.405...
and have higher late
mortality after discharge.66 Lafrance JP, Miller DR. Acute kidney injury associates with increased
long-term mortality. J Am Soc Nephrol 2010;21:345-52. DOI:
http://dx.doi.org/10.1681/ASN.2009060636
http://dx.doi.org/10.1681/ASN.2009060636...
7 Gammelager H, Christiansen CF, Johansen MB, Tønnesen E, Jespersen B,
Sørensen HT. One-year mortality among Danish intensive care patients with acute
kidney injury: a cohort study. Crit Care 2012;16:R124. DOI:
http://dx.doi.org/10.1186/cc11420
http://dx.doi.org/10.1186/cc11420...
8 Ponce D, Zorzenon Cde P, dos Santos NY, Balbi AL. Early nephrology
consultation can have an impact on outcome of acute kidney injury patients. Nephrol
Dial Transplant 2011;26:3202-6. DOI:
http://dx.doi.org/10.1093/ndt/gfr359
http://dx.doi.org/10.1093/ndt/gfr359...
9 Macedo E, Castro I, Yu L, Abdulkader RR, Vieira JM Jr. Impact of mild
acute kidney injury (AKI) on outcome after open repair of aortic aneurysms. Ren Fail
2008;30:287-96. DOI: http://dx.doi.org/10.1080/08860220701857522
http://dx.doi.org/10.1080/08860220701857...
-1010 United States Renal Data System USRDS 2012 Annual Data Report: Atlas of
CKD and ESRD in the United States. Am J Kidney Dis 2013;61:e1-e480. AKI prevention involves the identification of
its main causes. In the clinical context of ICU patients, AKI is predominantly
multifactorial in etiology: ischemic and/or nephrotoxic.1111 Santos WJ, Zanetta DM, Pires AC, Lobo SM, Lima EQ, Burdmann EA. Patients
with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care
unit-a homogeneous population? Crit Care 2006;10:R68. DOI:
http://dx.doi.org/10.1186/cc4904
http://dx.doi.org/10.1186/cc4904...
Sepsis is the cause of over 50% of AKI cases in the ICU
worldwide, followed by major surgery and low cardiac output.11 Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, et al.
Continuous renal replacement therapy: a worldwide practice survey. The beginning and
ending supportive therapy for the kidney (B.E.S.T. kidney) investigators. Intensive
Care Med 2007;33:1563-70.
2 Fang Y, Ding X, Zhong Y, Zou J, Teng J, Tang Y, et al. Acute kidney
injury in a Chinese hospitalized population. Blood Purif 2010;30:120-6. DOI:
http://dx.doi.org/10.1159/000319972
http://dx.doi.org/10.1159/000319972...
3 Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk
stratification, and outcomes. Kidney Int 2012;81:819-25. PMID: 21975865 DOI:
http://dx.doi.org/10.1038/ki.2011.339
http://dx.doi.org/10.1038/ki.2011.339...
4 Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute
kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442-8. PMID:
22113526 DOI: http://dx.doi.org/10.1038/ki.2011.379
http://dx.doi.org/10.1038/ki.2011.379...
5 Bucaloiu ID, Kirchner HL, Norfolk ER, Hartle JE 2nd, Perkins RM.
Increased risk of death and de novo chronic kidney disease following reversible acute
kidney injury. Kidney Int 2012;81:477-85. PMID: 22157656 DOI:
http://dx.doi.org/10.1038/ki.2011.405
http://dx.doi.org/10.1038/ki.2011.405...
6 Lafrance JP, Miller DR. Acute kidney injury associates with increased
long-term mortality. J Am Soc Nephrol 2010;21:345-52. DOI:
http://dx.doi.org/10.1681/ASN.2009060636
http://dx.doi.org/10.1681/ASN.2009060636...
7 Gammelager H, Christiansen CF, Johansen MB, Tønnesen E, Jespersen B,
Sørensen HT. One-year mortality among Danish intensive care patients with acute
kidney injury: a cohort study. Crit Care 2012;16:R124. DOI:
http://dx.doi.org/10.1186/cc11420
http://dx.doi.org/10.1186/cc11420...
8 Ponce D, Zorzenon Cde P, dos Santos NY, Balbi AL. Early nephrology
consultation can have an impact on outcome of acute kidney injury patients. Nephrol
Dial Transplant 2011;26:3202-6. DOI:
http://dx.doi.org/10.1093/ndt/gfr359
http://dx.doi.org/10.1093/ndt/gfr359...
9 Macedo E, Castro I, Yu L, Abdulkader RR, Vieira JM Jr. Impact of mild
acute kidney injury (AKI) on outcome after open repair of aortic aneurysms. Ren Fail
2008;30:287-96. DOI: http://dx.doi.org/10.1080/08860220701857522
http://dx.doi.org/10.1080/08860220701857...
-1010 United States Renal Data System USRDS 2012 Annual Data Report: Atlas of
CKD and ESRD in the United States. Am J Kidney Dis 2013;61:e1-e480. In all
these situations, volume expansion is the mainstay of prevention and therapeutic
management because it contributes to the restoration of peripheral perfusion and
attenuates drug-induced nephrotoxicity.33 Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk
stratification, and outcomes. Kidney Int 2012;81:819-25. PMID: 21975865 DOI:
http://dx.doi.org/10.1038/ki.2011.339
http://dx.doi.org/10.1038/ki.2011.339...
,1212 Schrier R. Fluid administration in critically ill patients with acute
kidney injury. Clin J Am Soc Nephrol 2010;5:733-9. DOI:
http://dx.doi.org/10.2215/CJN.00060110
http://dx.doi.org/10.2215/CJN.00060110...
13 Townsend DR, Bagshaw SM. New insights on intravenous fluids, diuretics
and acute kidney injury. Nephron Clin Pract 2008;109:c206-16. PMID: 18802369 DOI:
http://dx.doi.org/10.1159/000142930
http://dx.doi.org/10.1159/000142930...
14 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al.
Early goal-directed therapy in the treatment of severe sepsis and septic shock. N
Engl J Med 2001;345:1368-77. DOI:
http://dx.doi.org/10.1056/NEJMoa010307
http://dx.doi.org/10.1056/NEJMoa010307...
-1515 Venkataraman R, Kellum JA. Sepsis: update in the management. Adv Chronic
Kidney Dis 2013;20:6-13. DOI:
http://dx.doi.org/10.1053/j.ackd.2012.10.013
http://dx.doi.org/10.1053/j.ackd.2012.10...
In 2001, Rivers et al.1414 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al.
Early goal-directed therapy in the treatment of severe sepsis and septic shock. N
Engl J Med 2001;345:1368-77. DOI:
http://dx.doi.org/10.1056/NEJMoa010307
http://dx.doi.org/10.1056/NEJMoa010307...
demonstrated in a randomized controlled study
that early aggressive fluid resuscitation - driven by protocol with defined goals -
significantly decreased mortality in severe sepsis. Despite numerous criticisms
during these last 13 years after its publication,1515 Venkataraman R, Kellum JA. Sepsis: update in the management. Adv Chronic
Kidney Dis 2013;20:6-13. DOI:
http://dx.doi.org/10.1053/j.ackd.2012.10.013
http://dx.doi.org/10.1053/j.ackd.2012.10...
this study markedly influenced the treatment of septic patients, having
been adopted as a key recommendation in all publications from the Surviving
Sepsis Campaign.1616 Bion J, Jaeschke R, Thompson BT, Levy M, Dellinger RP. Surviving sepsis
campaign: international guidelines for management of severe sepsis and septic shock:
2008. Intensive Care Med. 2008;34:1163-4. DOI:
http://dx.doi.org/10.1007/s00134-008-1090-z
http://dx.doi.org/10.1007/s00134-008-109...
Currently,
there are three randomized, controlled clinical trials in progress, aiming to
reproduce Rivers's findings: one in the U.S. (Protocoled Care for Early Septic Shock
- Process), another in Australia (Australasian Resuscitation in Sepsis Evaluation
randomized Controlled Trial - ARISE) and the third in England. Although Rivers
et al. paper did explore the impact of volume resuscitation in
the prevention of AKI, Lin et al.1717 Lin SM, Huang CD, Lin HC, Liu CY, Wang CH, Kuo HP. A modified
goal-directed protocol improves clinical outcomes in intensive care unit patients
with septic shock: a randomized controlled trial. Shock 2006;26:551-7. PMID: 17117128
DOI: http://dx.doi.org/10.1097/01.shk.0000232271.09440.8f
http://dx.doi.org/10.1097/01.shk.0000232...
showed in a later study, that early fluid resuscitation, similar to
that used in the Rivers's protocol, reduced the incidence of AKI (55% to 39%,
p = 0.015) in patients with septic shock.
Thus, adequate fluid resuscitation within the first six hours of hospital care in
septic patients seems to be associated with prevention of tissue ischemia (including
renal ischemia) and increased survival. A positive fluid balance (FB+) for a short
period of time in patients undergoing resuscitation with these protocols can be the
cost to be paid to restore tissue perfusion. However, this liberal strategy of fluid
infusion after the first six hours of care can cause a continuously positive FB.
Indeed, this approach was not endorsed by Rivers;1414 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al.
Early goal-directed therapy in the treatment of severe sepsis and septic shock. N
Engl J Med 2001;345:1368-77. DOI:
http://dx.doi.org/10.1056/NEJMoa010307
http://dx.doi.org/10.1056/NEJMoa010307...
however the situation is common in current clinical practice,1818 Macedo E, Bouchard J, Soroko SH, Chertow GM, Himmelfarb J, Ikizler TA,
et al. Fluid accumulation, recognition and staging of acute kidney injury in
critically-ill patients. Crit Care 2010;14:R82. DOI:
http://dx.doi.org/10.1186/cc9004
http://dx.doi.org/10.1186/cc9004...
with deleterious consequences to the
patient.
It is also possible that the goal-oriented fluid resuscitation benefits are not due
only to the administration of larger volumes of fluids to patients who specifically
so require, in accordance with pre-established hemodynamic parameters, but the
earliness and suitability of this measure. Administration of fluids to the limited
optimization of hemodynamic parameters set previously could result in less volume of
fluid infusion, minimizing FB+.1919 Prowle JR, Chua HR, Bagshaw SM, Bellomo R. Clinical review: Volume of
fluid resuscitation and the incidence of acute kidney injury - a systematic review.
Crit Care 2012;16:230. DOI: http://dx.doi.org/10.1186/cc11345
http://dx.doi.org/10.1186/cc11345...
Tokarik
et al.2020 Tokarik M, Sjöberg F, Balik M, Pafcuga I, Broz L. Fluid therapy LiDCO
controlled trial-optimization of volume resuscitation of extensively burned patients
through noninvasive continuous real-time hemodynamic monitoring LiDCO. J Burn Care
Res 2013;34:537-42. DOI:
http://dx.doi.org/10.1097/BCR.0b013e318278197e
http://dx.doi.org/10.1097/BCR.0b013e3182...
piloted a study
with 21 burn patients and showed that fluid response determination using LiDCO
(Lithium Dilution Cardiac Output) during resuscitation enabled the administration of
less crystalloid volume. The study randomized two groups of burn patients: Group 1,
whose resuscitation was based on systolic pressure variation (SPV) measurements and
pulse pressure variation (PPV) with LiDCO; and Group 2, whose resuscitation was based
on commonly used formulas (modified Brooke/Parkland) for volume expansion in burn
patients. Group 1 received significantly less crystalloid than Group 2 (5090 ± 680 ml
and 7.820 ± 1.050 ml, respectively, p = 0.04).2020 Tokarik M, Sjöberg F, Balik M, Pafcuga I, Broz L. Fluid therapy LiDCO
controlled trial-optimization of volume resuscitation of extensively burned patients
through noninvasive continuous real-time hemodynamic monitoring LiDCO. J Burn Care
Res 2013;34:537-42. DOI:
http://dx.doi.org/10.1097/BCR.0b013e318278197e
http://dx.doi.org/10.1097/BCR.0b013e3182...
Thus, goal-oriented fluid resuscitation does not necessarily
imply larger infusions of fluid and excessively positive FB.1919 Prowle JR, Chua HR, Bagshaw SM, Bellomo R. Clinical review: Volume of
fluid resuscitation and the incidence of acute kidney injury - a systematic review.
Crit Care 2012;16:230. DOI: http://dx.doi.org/10.1186/cc11345
http://dx.doi.org/10.1186/cc11345...
,2020 Tokarik M, Sjöberg F, Balik M, Pafcuga I, Broz L. Fluid therapy LiDCO
controlled trial-optimization of volume resuscitation of extensively burned patients
through noninvasive continuous real-time hemodynamic monitoring LiDCO. J Burn Care
Res 2013;34:537-42. DOI:
http://dx.doi.org/10.1097/BCR.0b013e318278197e
http://dx.doi.org/10.1097/BCR.0b013e3182...
Positive fluid balance and ICU mortality: is FB+ harmful?
Patients with persistently positive FB are more subject to adverse clinical
consequences such as liver congestion, bowel edema with ileus, malabsorption,
abdominal compartment syndrome/intraabdominal hypertension, myocardial edema with
conduction abnormalities and diastolic dysfunction, pulmonary congestion with
worsening compliance and gas exchange, cerebral edema, kidney edema and peripheral
tissues edema with poor wound healing and infections (Chart 1).2121 Yohannes S, Chawla LS. Evolving practices in the management of acute
kidney injury in the ICU (Intensive Care Unit). Clin Nephrol 2009;71:602-7. DOI:
http://dx.doi.org/10.5414/CNP71602
http://dx.doi.org/10.5414/CNP71602...
22 Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD; National Heart,
Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Fluid balance,
diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol
2011;6:966-73. DOI: http://dx.doi.org/10.2215/CJN.08781010
http://dx.doi.org/10.2215/CJN.08781010...
23 Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R. Fluid balance
and acute kidney injury. Nat Rev Nephrol 2010;6:107-15. DOI:
http://dx.doi.org/10.1038/nrneph.2009.213
http://dx.doi.org/10.1038/nrneph.2009.21...
24 Bagshaw SM, Brophy PD, Cruz D, Ronco C. Fluid balance as a biomarker:
impact of fluid overload on outcome in critically ill patients with acute kidney
injury. Crit Care 2008;12:169. DOI: http://dx.doi.org/10.1186/cc6948
http://dx.doi.org/10.1186/cc6948...
-2525 Bouchard J, Mehta RL. Fluid accumulation and acute kidney injury:
consequence or cause. Curr Opin Crit Care 2009;15:509-13. DOI:
http://dx.doi.org/10.1097/MCC.0b013e328332f653
http://dx.doi.org/10.1097/MCC.0b013e3283...
Encapsulated
organs such as the kidney and liver, have limited capacity to accommodate excess
fluid, which can determine increased interstitial pressure with consequent impairment
of blood flow and functional deterioration.1313 Townsend DR, Bagshaw SM. New insights on intravenous fluids, diuretics
and acute kidney injury. Nephron Clin Pract 2008;109:c206-16. PMID: 18802369 DOI:
http://dx.doi.org/10.1159/000142930
http://dx.doi.org/10.1159/000142930...
,2222 Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD; National Heart,
Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Fluid balance,
diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol
2011;6:966-73. DOI: http://dx.doi.org/10.2215/CJN.08781010
http://dx.doi.org/10.2215/CJN.08781010...
Increased kidney
interstitial pressure in patients with buildup FB+ cause blood hypoperfusion and
decreased glomerular filtration. Moreover, the increase in intraabdominal pressure
(IAP), central venous pressure (CVP) and kidney venous pressure (KVP) increases, in
conditions of fluid overload substantially contributes to the decline in glomerular
filtration rate, as suggested by experimental studies. Kidney venous pressure above
30 mmHg for 2 hours in intact porcine kidneys results in a significant decline in
kidney plasma flow and glomerular filtration rate.2626 Doty JM, Saggi BH, Sugerman HJ, Blocher CR, Pin R, Fakhry I, et al.
Effect of increased renal venous pressure on renal function J Trauma 1999;47:1000-3.
PMID: 10608524 DOI:
http://dx.doi.org/10.1097/00005373-199901000-00057
http://dx.doi.org/10.1097/00005373-19990...
KVP elevation limited renal blood flow and urine formation more than
arterial blood hypoperfusion.2626 Doty JM, Saggi BH, Sugerman HJ, Blocher CR, Pin R, Fakhry I, et al.
Effect of increased renal venous pressure on renal function J Trauma 1999;47:1000-3.
PMID: 10608524 DOI:
http://dx.doi.org/10.1097/00005373-199901000-00057
http://dx.doi.org/10.1097/00005373-19990...
,2727 Lazzeri C, Valente S, Tarquini R, Gensini GF. Cardiorenal syndrome
caused by heart failure with preserved ejection fraction Int J Nephrol
2011;2011:634903. PMID: 21331316 DOI:
http://dx.doi.org/10.4061/2011/634903
http://dx.doi.org/10.4061/2011/634903...
In patients with
cardiorenal syndrome, with or without low cardiac output, elevation of CVP, KVP IAP
may contribute to progressive kidney dysfunction.2727 Lazzeri C, Valente S, Tarquini R, Gensini GF. Cardiorenal syndrome
caused by heart failure with preserved ejection fraction Int J Nephrol
2011;2011:634903. PMID: 21331316 DOI:
http://dx.doi.org/10.4061/2011/634903
http://dx.doi.org/10.4061/2011/634903...
And in patients undergoing elective cardiac surgery, having a high CVP
is a strong predictor of postoperative AKI, regardless of low heart output.2727 Lazzeri C, Valente S, Tarquini R, Gensini GF. Cardiorenal syndrome
caused by heart failure with preserved ejection fraction Int J Nephrol
2011;2011:634903. PMID: 21331316 DOI:
http://dx.doi.org/10.4061/2011/634903
http://dx.doi.org/10.4061/2011/634903...
,2828 Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, et al.
Cardiorenal interactions: insights from the ESCAPE trial. J Am Coll Cardiol
2008;51:1268-74. DOI: http://dx.doi.org/10.1016/j.jacc.2007.08.072
http://dx.doi.org/10.1016/j.jacc.2007.08...
Under physiological conditions, IAP ranges from sub atmospheric to 0 mmHg. Prolonged
elevated IAP or above 12 mmHg defines intraabdominal hypertension. Levels of IAP
between 10 and 15 mmHg cause a reduction in mesenteric perfusion with ischemia,
inflammation, and more swelling, which in turn enhances the intraabdominal pressure,
closing the cycle. When the IAP achieves 20 mmHg, there is an increase in the chances
of systemic clinical consequences, such as cardiovascular disorders (increased CVP,
decreased venous return and cardiac output), kidney disorders (decreased renal plasma
flow, increased KVP, renal microvascular congestion, increased renal vascular
resistance, elevated catecholamines, angiotensin II, inflammatory cytokines and renal
capsule hypertension), lung (reduced chest wall compliance, increased KVP, increased
dead space, hypercapnia and hypoxia) and cerebral (increased intracranial pressure
and decreased cerebral perfusion pressure), configuring an abdominal compartment
syndrome.2929 Dalfino L, Sicolo A, Paparella D, Mongelli M, Rubino G, Brienza N.
Intra-abdominal hypertension in cardiac surgery. Interact Cardiovasc Thorac Surg
2013;17:644-51. DOI: http://dx.doi.org/10.1093/icvts/ivt272
http://dx.doi.org/10.1093/icvts/ivt272...
,3030 Cheatham ML, Malbrain ML, Kirkpatrick A, Sugrue M, Parr M, De Waele J,
et al. Results from the International Conference of Experts on Intra-abdominal
Hypertension and Abdominal Compartment Syndrome. II. Recommendations. Intensive Care
Med 2007;33:951-62. Primarily, the abdominal compartment syndrome
was described in patients undergoing abdominal surgery or trauma victims; however,
currently, it is increasingly diagnosed in patients undergoing massive fluid
resuscitation, multiple transfusions, hypothermia or coagulation disorders, i.e.,
patients with successive FB+. There is evidence that intraabdominal hypertension
present at ICU admission is associated with increased risk of severe organ
dysfunction (including AKI) and the highest mortality.2929 Dalfino L, Sicolo A, Paparella D, Mongelli M, Rubino G, Brienza N.
Intra-abdominal hypertension in cardiac surgery. Interact Cardiovasc Thorac Surg
2013;17:644-51. DOI: http://dx.doi.org/10.1093/icvts/ivt272
http://dx.doi.org/10.1093/icvts/ivt272...
,3030 Cheatham ML, Malbrain ML, Kirkpatrick A, Sugrue M, Parr M, De Waele J,
et al. Results from the International Conference of Experts on Intra-abdominal
Hypertension and Abdominal Compartment Syndrome. II. Recommendations. Intensive Care
Med 2007;33:951-62.
Another no less important aspect, which may contribute to the adverse outcomes
associated with FB+, is the type of solution used for fluid resuscitation. Synthetic
colloids are potentially nephrotoxic and are associated with increased mortality,
especially HES solutions (hydroxyethyl starch) and possibly gelatins.3131 Prowle JR, Bellomo R. Fluid administration and the kidney. Curr Opin
Crit Care 2013;19:308-14. DOI:
http://dx.doi.org/10.1097/MCC.0b013e3283632e29
http://dx.doi.org/10.1097/MCC.0b013e3283...
32 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice
Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:S1-138.-3333 Severs D, Hoorn EJ, Rookmaaker MB. A critical appraisal of intravenous
fluids: from the physiological basis to clinical evidence. Nephrol Dial Transplant
2014 Jan 23. [Epub ahead of print] DOI:
http://dx.doi.org/10.1093/ndt/gfu005
http://dx.doi.org/10.1093/ndt/gfu005...
4% albumin should be avoided in the fluid resuscitation of patients
with head injury, but appears to be safe in AKI septic patients or at risk of
developing it.3131 Prowle JR, Bellomo R. Fluid administration and the kidney. Curr Opin
Crit Care 2013;19:308-14. DOI:
http://dx.doi.org/10.1097/MCC.0b013e3283632e29
http://dx.doi.org/10.1097/MCC.0b013e3283...
32 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice
Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:S1-138.-3333 Severs D, Hoorn EJ, Rookmaaker MB. A critical appraisal of intravenous
fluids: from the physiological basis to clinical evidence. Nephrol Dial Transplant
2014 Jan 23. [Epub ahead of print] DOI:
http://dx.doi.org/10.1093/ndt/gfu005
http://dx.doi.org/10.1093/ndt/gfu005...
The use of 20% albumin has been associated
with lower incidence of AKI and reduced mortality in cirrhotic patients with
spontaneous bacterial peritonitis, but its routine use ends up being limited by the
higher cost of crystalloid.3434 Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, et
al. Effect of intravenous albumin on renal impairment and mortality in patients with
cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-9. PMID:
10432325 DOI: http://dx.doi.org/10.1056/NEJM199908053410603
http://dx.doi.org/10.1056/NEJM1999080534...
Thus, the Kidney
Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for AKI in its
latest edition, suggests that isotonic crystalloids are preferable, instead of
synthetic or non-synthetic colloids for volume expansion in patients at risk of
developing AKI or AKI installed in the absence of a hemorrhagic shock.3232 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice
Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:S1-138.
However, crystalloids are not without risk. Clinical and experimental studies suggest
that unbalanced crystalloid or with higher chlorine content may worsen metabolic
acidosis, cause kidney vasoconstriction and reduce the kidney oxygen
consumption.3535 Aksu U, Bezemer R, Yavuz B, Kandil A, Demirci C, Ince C. Balanced vs
unbalanced crystalloid resuscitation in a near-fatal model of hemorrhagic shock and
the effects on renal oxygenation, oxidative stress, and inflammation. Resuscitation
2012;83:767-73. DOI:
http://dx.doi.org/10.1016/j.resuscitation.2011.11.022
http://dx.doi.org/10.1016/j.resuscitatio...
36 Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled,
double-blind crossover study on the effects of 2-L infusions of 0.9% saline and
plasma-lyte((r)) 148 on renal blood flow velocity and renal cortical tissue perfusion
in healthy volunteers. Ann Surg 2012;256:18-24. PMID: 22580944 DOI:
http://dx.doi.org/10.1097/SLA.0b013e318256be72
http://dx.doi.org/10.1097/SLA.0b013e3182...
-3737 Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association
between a chloride-liberal vs chloride-restrictive intravenous fluid administration
strategy and kidney injury in critically ill adults. JAMA 2012;308:1566-72. PMID:
23073953 DOI: http://dx.doi.org/10.1001/jama.2012.13356
http://dx.doi.org/10.1001/jama.2012.1335...
Chowdhury et al.3636 Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled,
double-blind crossover study on the effects of 2-L infusions of 0.9% saline and
plasma-lyte((r)) 148 on renal blood flow velocity and renal cortical tissue perfusion
in healthy volunteers. Ann Surg 2012;256:18-24. PMID: 22580944 DOI:
http://dx.doi.org/10.1097/SLA.0b013e318256be72
http://dx.doi.org/10.1097/SLA.0b013e3182...
led a crossover study in healthy volunteers,
randomized to receiving alternating 2 liters of isotonic 0.9% saline (containing 150
mmol/l chlorine) and 2 liters of Plasmalyte (containing 98 mmol/l chloride) IV. Upon
receiving isotonic saline 0.9%, individuals took longer to have the first urination
(from 90 to 142 min, p = 0.006), reduced urine volume of 833 ml to
523 ml (p = 0.002) and reduced kidney plasma flow velocity and
kidney cortical perfusion assessed by MRI.3636 Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled,
double-blind crossover study on the effects of 2-L infusions of 0.9% saline and
plasma-lyte((r)) 148 on renal blood flow velocity and renal cortical tissue perfusion
in healthy volunteers. Ann Surg 2012;256:18-24. PMID: 22580944 DOI:
http://dx.doi.org/10.1097/SLA.0b013e318256be72
http://dx.doi.org/10.1097/SLA.0b013e3182...
Yunos et al.3737 Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association
between a chloride-liberal vs chloride-restrictive intravenous fluid administration
strategy and kidney injury in critically ill adults. JAMA 2012;308:1566-72. PMID:
23073953 DOI: http://dx.doi.org/10.1001/jama.2012.13356
http://dx.doi.org/10.1001/jama.2012.1335...
conducted a
prospective, controlled pilot study in critically ill patients, comparing the liberal
strategy of fluid infusion containing chlorine (as gelatin and 0.9% saline) with the
use of balanced solutions or with less chlorine content such as Hartmann's solution
(containing 109 mmol/l chlorine) and Plasmalyte. Fluid handling with balanced
solutions reduced the frequency of hyperchloremia, metabolic acidosis and was
associated with significant reduction in the incidence of AKI and need for supportive
kidney therapy.3737 Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association
between a chloride-liberal vs chloride-restrictive intravenous fluid administration
strategy and kidney injury in critically ill adults. JAMA 2012;308:1566-72. PMID:
23073953 DOI: http://dx.doi.org/10.1001/jama.2012.13356
http://dx.doi.org/10.1001/jama.2012.1335...
Therefore, not only the
amount of fluid infused in the volume resuscitation, but also its composition, can
interfere with unfavorable outcomes associated with FB+.
All these deleterious consequences of FB+ have been associated with increased
mortality in critically ill patients.3838 National Heart, Lung, and Blood Institute Acute Respiratory Distress
Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR,
Thompson BT, Hayden D, deBoisblanc B, et al. Comparison of two fluid-management
strategies in acute lung injury. N Engl J Med 2006;354:2564-75. PMID: 16714767 DOI:
http://dx.doi.org/10.1056/NEJMoa062200
http://dx.doi.org/10.1056/NEJMoa062200...
39 Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR. A
randomized, controlled trial of furosemide with or without albumin in hypoproteinemic
patients with acute lung injury. Crit Care Med 2005;33:1681-7. PMID: 16096441 DOI:
http://dx.doi.org/10.1097/01.CCM.0000171539.47006.02
http://dx.doi.org/10.1097/01.CCM.0000171...
40 Mitchell JP, Schuller D, Calandrino FS, Schuster DP. Improved outcome
based on fluid management in critically ill patients requiring pulmonary artery
catheterization. Am Rev Respir Dis 1992;145:990-8. PMID: 1586077 DOI:
http://dx.doi.org/10.1164/ajrccm/145.5.990
http://dx.doi.org/10.1164/ajrccm/145.5.9...
41 Brandstrup B, Tønnesen H, Beier-Holgersen R, Hjortsø E, Ørding H,
Lindorff-Larsen K, et al. Effects of intravenous fluid restriction on postoperative
complications: comparison of two perioperative fluid regimens: a randomized
assessor-blinded multicenter trial. Ann Surg 2003;238:641-8. PMID: 14578723 DOI:
http://dx.doi.org/10.1097/01.sla.0000094387.50865.23
http://dx.doi.org/10.1097/01.sla.0000094...
42 Vidal MG, Ruiz Weisser J, Gonzalez F, Toro MA, Loudet C, Balasini C, et
al. Incidence and clinical effects of intra-abdominal hypertension in critically ill
patients. Crit Care Med 2008;36:1823-31. DOI:
http://dx.doi.org/10.1097/CCM.0b013e31817c7a4d
http://dx.doi.org/10.1097/CCM.0b013e3181...
43 Adesanya A, Rosero E, Timaran C, Clagett P, Johnston WE. Intraoperative
fluid restriction predicts improved outcomes in major vascular surgery. Vasc
Endovascular Surg 2008;42:531-6. PMID: 18583299 DOI:
http://dx.doi.org/10.1177/1538574408318474
http://dx.doi.org/10.1177/15385744083184...
44 McArdle GT, McAuley DF, McKinley A, Blair P, Hoper M, Harkin DW.
Preliminary results of a prospective randomized trial of restrictive versus standard
fluid regime in elective open abdominal aortic aneurysm repair. Ann Surg
2009;250:28-34. PMID: 19561485 DOI:
http://dx.doi.org/10.1097/SLA.0b013e3181ad61c8
http://dx.doi.org/10.1097/SLA.0b013e3181...
45 Arlati S, Storti E, Pradella V, Bucci L, Vitolo A, Pulici M. Decreased
fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A
preliminary study. Resuscitation 2007;72:371-8. PMID: 17137702 DOI:
http://dx.doi.org/10.1016/j.resuscitation.2006.07.010
http://dx.doi.org/10.1016/j.resuscitatio...
46 Goldstein SL, Currier H, Graf Cd, Cosio CC, Brewer ED, Sachdeva R.
Outcome in children receiving continuous venovenous hemofiltration. Pediatrics
2001;107:1309-12. DOI: http://dx.doi.org/10.1542/peds.107.6.1309
http://dx.doi.org/10.1542/peds.107.6.130...
47 Goldstein SL, Somers MJ, Baum MA, Symons JM, Brophy PD, Blowey D, et al.
Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal
replacement therapy. Kidney Int 2005;67:653-8. PMID: 15673313 DOI:
http://dx.doi.org/10.1111/j.1523-1755.2005.67121.x
http://dx.doi.org/10.1111/j.1523-1755.20...
48 Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard
ML, et al. Fluid overload before continuous hemofiltration and survival in critically
ill children: a retrospective analysis. Crit Care Med 2004;32:1771-6. DOI:
http://dx.doi.org/10.1097/01.CCM.0000132897.52737.49
http://dx.doi.org/10.1097/01.CCM.0000132...
49 Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini
EP, et al.; Program to Improve Care in Acute Renal Disease (PICARD) Study Group.
Fluid accumulation, survival and recovery of kidney function in critically ill
patients with acute kidney injury. Kidney Int 2009;76:422-7.
50 Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et
al.; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European
intensive care units: results of the SOAP study. Crit Care Med 2006;34:344-53. DOI:
http://dx.doi.org/10.1097/01.CCM.0000194725.48928.3A
http://dx.doi.org/10.1097/01.CCM.0000194...
51 Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL; Sepsis
Occurrence in Acutely Ill Patients (SOAP) Investigators. A positive fluid balance is
associated with a worse outcome in patients with acute renal failure. Crit Care
2008;12:R74. DOI: http://dx.doi.org/10.1186/cc6916
http://dx.doi.org/10.1186/cc6916...
52 de Almeida JP, Palomba H, Galas FR, Fukushima JT, Duarte FA, Nagaoka D,
et al. Positive fluid balance is associated with reduced survival in critically ill
patients with cancer. Acta Anaesthesiol Scand 2012;56:712-7. DOI:
http://dx.doi.org/10.1111/j.1399-6576.2012.02717.x
http://dx.doi.org/10.1111/j.1399-6576.20...
53 Vaara ST, Korhonen AM, Kaukonen KM, Nisula S, Inkinen O, Hoppu S, et
al.; The FINNAKI study group. Fluid overload is associated with an increased risk for
90-day mortality in critically ill patients with renal replacement therapy: data from
the prospective FINNAKI study. Crit Care 2012;16:R197. DOI:
http://dx.doi.org/10.1186/cc11682
http://dx.doi.org/10.1186/cc11682...
-5454 Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, et
al.; FEAST Trial Group. Mortality after fluid bolus in African children with severe
infection. N Engl J Med 2011;364:2483-95. PMID: 21615299 DOI:
http://dx.doi.org/10.1056/NEJMoa1101549
http://dx.doi.org/10.1056/NEJMoa1101549...
Tables 1 and 2 summarize the most important studies that sought to assess the impact of
FB+ in the morbidity and mortality of critically ill patients.3838 National Heart, Lung, and Blood Institute Acute Respiratory Distress
Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR,
Thompson BT, Hayden D, deBoisblanc B, et al. Comparison of two fluid-management
strategies in acute lung injury. N Engl J Med 2006;354:2564-75. PMID: 16714767 DOI:
http://dx.doi.org/10.1056/NEJMoa062200
http://dx.doi.org/10.1056/NEJMoa062200...
39 Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR. A
randomized, controlled trial of furosemide with or without albumin in hypoproteinemic
patients with acute lung injury. Crit Care Med 2005;33:1681-7. PMID: 16096441 DOI:
http://dx.doi.org/10.1097/01.CCM.0000171539.47006.02
http://dx.doi.org/10.1097/01.CCM.0000171...
40 Mitchell JP, Schuller D, Calandrino FS, Schuster DP. Improved outcome
based on fluid management in critically ill patients requiring pulmonary artery
catheterization. Am Rev Respir Dis 1992;145:990-8. PMID: 1586077 DOI:
http://dx.doi.org/10.1164/ajrccm/145.5.990
http://dx.doi.org/10.1164/ajrccm/145.5.9...
41 Brandstrup B, Tønnesen H, Beier-Holgersen R, Hjortsø E, Ørding H,
Lindorff-Larsen K, et al. Effects of intravenous fluid restriction on postoperative
complications: comparison of two perioperative fluid regimens: a randomized
assessor-blinded multicenter trial. Ann Surg 2003;238:641-8. PMID: 14578723 DOI:
http://dx.doi.org/10.1097/01.sla.0000094387.50865.23
http://dx.doi.org/10.1097/01.sla.0000094...
42 Vidal MG, Ruiz Weisser J, Gonzalez F, Toro MA, Loudet C, Balasini C, et
al. Incidence and clinical effects of intra-abdominal hypertension in critically ill
patients. Crit Care Med 2008;36:1823-31. DOI:
http://dx.doi.org/10.1097/CCM.0b013e31817c7a4d
http://dx.doi.org/10.1097/CCM.0b013e3181...
43 Adesanya A, Rosero E, Timaran C, Clagett P, Johnston WE. Intraoperative
fluid restriction predicts improved outcomes in major vascular surgery. Vasc
Endovascular Surg 2008;42:531-6. PMID: 18583299 DOI:
http://dx.doi.org/10.1177/1538574408318474
http://dx.doi.org/10.1177/15385744083184...
44 McArdle GT, McAuley DF, McKinley A, Blair P, Hoper M, Harkin DW.
Preliminary results of a prospective randomized trial of restrictive versus standard
fluid regime in elective open abdominal aortic aneurysm repair. Ann Surg
2009;250:28-34. PMID: 19561485 DOI:
http://dx.doi.org/10.1097/SLA.0b013e3181ad61c8
http://dx.doi.org/10.1097/SLA.0b013e3181...
45 Arlati S, Storti E, Pradella V, Bucci L, Vitolo A, Pulici M. Decreased
fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A
preliminary study. Resuscitation 2007;72:371-8. PMID: 17137702 DOI:
http://dx.doi.org/10.1016/j.resuscitation.2006.07.010
http://dx.doi.org/10.1016/j.resuscitatio...
46 Goldstein SL, Currier H, Graf Cd, Cosio CC, Brewer ED, Sachdeva R.
Outcome in children receiving continuous venovenous hemofiltration. Pediatrics
2001;107:1309-12. DOI: http://dx.doi.org/10.1542/peds.107.6.1309
http://dx.doi.org/10.1542/peds.107.6.130...
47 Goldstein SL, Somers MJ, Baum MA, Symons JM, Brophy PD, Blowey D, et al.
Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal
replacement therapy. Kidney Int 2005;67:653-8. PMID: 15673313 DOI:
http://dx.doi.org/10.1111/j.1523-1755.2005.67121.x
http://dx.doi.org/10.1111/j.1523-1755.20...
48 Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard
ML, et al. Fluid overload before continuous hemofiltration and survival in critically
ill children: a retrospective analysis. Crit Care Med 2004;32:1771-6. DOI:
http://dx.doi.org/10.1097/01.CCM.0000132897.52737.49
http://dx.doi.org/10.1097/01.CCM.0000132...
49 Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini
EP, et al.; Program to Improve Care in Acute Renal Disease (PICARD) Study Group.
Fluid accumulation, survival and recovery of kidney function in critically ill
patients with acute kidney injury. Kidney Int 2009;76:422-7.
50 Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et
al.; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European
intensive care units: results of the SOAP study. Crit Care Med 2006;34:344-53. DOI:
http://dx.doi.org/10.1097/01.CCM.0000194725.48928.3A
http://dx.doi.org/10.1097/01.CCM.0000194...
51 Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL; Sepsis
Occurrence in Acutely Ill Patients (SOAP) Investigators. A positive fluid balance is
associated with a worse outcome in patients with acute renal failure. Crit Care
2008;12:R74. DOI: http://dx.doi.org/10.1186/cc6916
http://dx.doi.org/10.1186/cc6916...
52 de Almeida JP, Palomba H, Galas FR, Fukushima JT, Duarte FA, Nagaoka D,
et al. Positive fluid balance is associated with reduced survival in critically ill
patients with cancer. Acta Anaesthesiol Scand 2012;56:712-7. DOI:
http://dx.doi.org/10.1111/j.1399-6576.2012.02717.x
http://dx.doi.org/10.1111/j.1399-6576.20...
53 Vaara ST, Korhonen AM, Kaukonen KM, Nisula S, Inkinen O, Hoppu S, et
al.; The FINNAKI study group. Fluid overload is associated with an increased risk for
90-day mortality in critically ill patients with renal replacement therapy: data from
the prospective FINNAKI study. Crit Care 2012;16:R197. DOI:
http://dx.doi.org/10.1186/cc11682
http://dx.doi.org/10.1186/cc11682...
-5454 Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, et
al.; FEAST Trial Group. Mortality after fluid bolus in African children with severe
infection. N Engl J Med 2011;364:2483-95. PMID: 21615299 DOI:
http://dx.doi.org/10.1056/NEJMoa1101549
http://dx.doi.org/10.1056/NEJMoa1101549...
Bouchard et al.4949 Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, et al.; Program to Improve Care in Acute Renal Disease (PICARD) Study Group. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 2009;76:422-7. evaluated the adult population with AKI in the PICARD study and found that, at the time of AKI diagnosis, the percentage of fluid accumulation in relation to the patient's weight upon ICU admission was lower in survivors than in nonsurvivors (p = 0.01). However, this difference was not statistically significant after adjustment for APACHE III (p = 0.12) scores. When the rate of fluid accumulation from all patients was greater than 10% - featuring fluid overload, mortality at 30 and 60 days rose from 25 to 37% (p = 0.02) and 35 to 48% (p = 0.01), respectively. The risk of death associated with fluid overload in dialysis patients was 2.07 (95% CI 1.27 to 3.37), adjusted for severity of illness and dialysis modality. In patients not on dialysis with fluid overload, the risk of death was 3.14 (95% CI 1.18 to 8.33). Patients who kept fluid accumulation during hospitalization had higher mortality, which was proportional to fluid buildup (p < 0.0001). Patients in whom dialysis was able to correct fluid overload had lower mortality than those who remained with fluid overload after dialysis (35% vs. 56% respectively, p = 0.002). The adjusted risk of death associated with fluid overload at the end of dialysis was 2.52 (95% CI 1.55 to 4.08). Patients with fluid overload at the time that creatinine was higher were less likely to recover kidney function (35% vs. 52% respectively, p = 0.007). This latter finding suggests that, after AKI installing, the administration of excess fluid exerts no protective effect on kidney recovery. However, it is not possible to say that the fluid overload per se was the cause of delayed kidney recovery, or if patients with fluid overload already had a more severe AKI, and therefore also had a later recovery.37
By means of a multicenter prospective observational study with 296 patients from 17
ICUs, Vaara ST et al.,5353 Vaara ST, Korhonen AM, Kaukonen KM, Nisula S, Inkinen O, Hoppu S, et
al.; The FINNAKI study group. Fluid overload is associated with an increased risk for
90-day mortality in critically ill patients with renal replacement therapy: data from
the prospective FINNAKI study. Crit Care 2012;16:R197. DOI:
http://dx.doi.org/10.1186/cc11682
http://dx.doi.org/10.1186/cc11682...
also
reported that fluid overload (defined as fluid accumulation above 10% of the baseline
weight) at the time of the Renal Support Therapy (RST) indication, was associated
with a higher risk of death at 90 days (OR 2.6), after adjustment for severity of
illness, RST onset time, RST modality and sepsis.5353 Vaara ST, Korhonen AM, Kaukonen KM, Nisula S, Inkinen O, Hoppu S, et
al.; The FINNAKI study group. Fluid overload is associated with an increased risk for
90-day mortality in critically ill patients with renal replacement therapy: data from
the prospective FINNAKI study. Crit Care 2012;16:R197. DOI:
http://dx.doi.org/10.1186/cc11682
http://dx.doi.org/10.1186/cc11682...
Although the association between FB+ and mortality seems logical and
likely, most of the studies that demonstrated it are observational in design, not
being able to establish definitive cause and effect relation.4040 Mitchell JP, Schuller D, Calandrino FS, Schuster DP. Improved outcome
based on fluid management in critically ill patients requiring pulmonary artery
catheterization. Am Rev Respir Dis 1992;145:990-8. PMID: 1586077 DOI:
http://dx.doi.org/10.1164/ajrccm/145.5.990
http://dx.doi.org/10.1164/ajrccm/145.5.9...
,4242 Vidal MG, Ruiz Weisser J, Gonzalez F, Toro MA, Loudet C, Balasini C, et
al. Incidence and clinical effects of intra-abdominal hypertension in critically ill
patients. Crit Care Med 2008;36:1823-31. DOI:
http://dx.doi.org/10.1097/CCM.0b013e31817c7a4d
http://dx.doi.org/10.1097/CCM.0b013e3181...
,4343 Adesanya A, Rosero E, Timaran C, Clagett P, Johnston WE. Intraoperative
fluid restriction predicts improved outcomes in major vascular surgery. Vasc
Endovascular Surg 2008;42:531-6. PMID: 18583299 DOI:
http://dx.doi.org/10.1177/1538574408318474
http://dx.doi.org/10.1177/15385744083184...
,4545 Arlati S, Storti E, Pradella V, Bucci L, Vitolo A, Pulici M. Decreased
fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A
preliminary study. Resuscitation 2007;72:371-8. PMID: 17137702 DOI:
http://dx.doi.org/10.1016/j.resuscitation.2006.07.010
http://dx.doi.org/10.1016/j.resuscitatio...
46 Goldstein SL, Currier H, Graf Cd, Cosio CC, Brewer ED, Sachdeva R.
Outcome in children receiving continuous venovenous hemofiltration. Pediatrics
2001;107:1309-12. DOI: http://dx.doi.org/10.1542/peds.107.6.1309
http://dx.doi.org/10.1542/peds.107.6.130...
47 Goldstein SL, Somers MJ, Baum MA, Symons JM, Brophy PD, Blowey D, et al.
Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal
replacement therapy. Kidney Int 2005;67:653-8. PMID: 15673313 DOI:
http://dx.doi.org/10.1111/j.1523-1755.2005.67121.x
http://dx.doi.org/10.1111/j.1523-1755.20...
48 Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard
ML, et al. Fluid overload before continuous hemofiltration and survival in critically
ill children: a retrospective analysis. Crit Care Med 2004;32:1771-6. DOI:
http://dx.doi.org/10.1097/01.CCM.0000132897.52737.49
http://dx.doi.org/10.1097/01.CCM.0000132...
49 Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini
EP, et al.; Program to Improve Care in Acute Renal Disease (PICARD) Study Group.
Fluid accumulation, survival and recovery of kidney function in critically ill
patients with acute kidney injury. Kidney Int 2009;76:422-7.
50 Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et
al.; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European
intensive care units: results of the SOAP study. Crit Care Med 2006;34:344-53. DOI:
http://dx.doi.org/10.1097/01.CCM.0000194725.48928.3A
http://dx.doi.org/10.1097/01.CCM.0000194...
51 Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL; Sepsis
Occurrence in Acutely Ill Patients (SOAP) Investigators. A positive fluid balance is
associated with a worse outcome in patients with acute renal failure. Crit Care
2008;12:R74. DOI: http://dx.doi.org/10.1186/cc6916
http://dx.doi.org/10.1186/cc6916...
52 de Almeida JP, Palomba H, Galas FR, Fukushima JT, Duarte FA, Nagaoka D,
et al. Positive fluid balance is associated with reduced survival in critically ill
patients with cancer. Acta Anaesthesiol Scand 2012;56:712-7. DOI:
http://dx.doi.org/10.1111/j.1399-6576.2012.02717.x
http://dx.doi.org/10.1111/j.1399-6576.20...
-5353 Vaara ST, Korhonen AM, Kaukonen KM, Nisula S, Inkinen O, Hoppu S, et
al.; The FINNAKI study group. Fluid overload is associated with an increased risk for
90-day mortality in critically ill patients with renal replacement therapy: data from
the prospective FINNAKI study. Crit Care 2012;16:R197. DOI:
http://dx.doi.org/10.1186/cc11682
http://dx.doi.org/10.1186/cc11682...
None of these studies can clarify whether patients with FB+ have higher
mortality for being more severe (and therefore require greater investment on drugs,
antibiotics, sedatives, parenteral nutrition etc.) or whether the FB+ has a really
independent pathophysiological involvement in the death process. Alternatively, we
can speculate that FB+ is an early biomarker of AKI, which is associated with
mortality (Figure 1).
Possible associations between acute kidney injury (AKI), positive fluid balance (FB+) and mortality. The FB+ may be associated with increased mortality for several pathophysiological pathways (blue arrows): to cause visceral and peripheral edema, making the organic functioning difficult; by dilution of hydrophilic antibiotics, reducing their effectiveness, or even by hemodilution of serum creatinine, delaying diagnosis of acute kidney injury (AKI). However, the FB+ is more often found in patients with higher clinical severity (orange arrow) and in patients with AKF (red arrow), both situations already independently associated with increased mortality.
There are only a few randomized clinical trials that studied the association between
mortality and FB+. Wiedemann et al.3838 National Heart, Lung, and Blood Institute Acute Respiratory Distress
Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR,
Thompson BT, Hayden D, deBoisblanc B, et al. Comparison of two fluid-management
strategies in acute lung injury. N Engl J Med 2006;354:2564-75. PMID: 16714767 DOI:
http://dx.doi.org/10.1056/NEJMoa062200
http://dx.doi.org/10.1056/NEJMoa062200...
randomized 1,000 patients with acute respiratory distress syndrome
(ARDS) into two fluid management strategies, one conservative and the other liberal.
This is the largest prospective, controlled study evaluating the impact of fluid
overload on the duration of mechanical ventilation and mortality in ARDS. The
conservative strategy of fluid infusion reduced the duration of mechanical
ventilation, without worsening kidney function; however, mortality was similar in
both grupos.3838 National Heart, Lung, and Blood Institute Acute Respiratory Distress
Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR,
Thompson BT, Hayden D, deBoisblanc B, et al. Comparison of two fluid-management
strategies in acute lung injury. N Engl J Med 2006;354:2564-75. PMID: 16714767 DOI:
http://dx.doi.org/10.1056/NEJMoa062200
http://dx.doi.org/10.1056/NEJMoa062200...
The largest randomized controlled trial designed to evaluate the impact of strategies
for fluid resuscitation on mortality was developed in six clinical centers in
Africa.5454 Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, et
al.; FEAST Trial Group. Mortality after fluid bolus in African children with severe
infection. N Engl J Med 2011;364:2483-95. PMID: 21615299 DOI:
http://dx.doi.org/10.1056/NEJMoa1101549
http://dx.doi.org/10.1056/NEJMoa1101549...
The authors studied septic
children (< 12 years of age) with signs of peripheral hypoperfusion who were
randomized to resuscitation with a bolus of saline (20 ml/kg IV at 1 hour), albumin
bolus (20 ml/kg IV at 1 hour) or no bolus (control). The three groups equally
received 2.5 to 4 ml/kg/h as maintenance fluids, blood transfusions if hemoglobin was
below 5 g/dL and appropriate antibiotics. Children with gastroenteritis, severe
malnutrition and shock of noninfectious causes were excluded. Children with severe
hypotension were randomized to saline bolus or albumin, with no control group. The
48-hour mortality was higher in the groups receiving intravenous bolus of 0.9% saline
or albumin compared to the group who received bolus (11% both groups
versus 7% bolus, RR 1.45, p = 0.003).5454 Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, et
al.; FEAST Trial Group. Mortality after fluid bolus in African children with severe
infection. N Engl J Med 2011;364:2483-95. PMID: 21615299 DOI:
http://dx.doi.org/10.1056/NEJMoa1101549
http://dx.doi.org/10.1056/NEJMoa1101549...
No FB data from each group was shown.
Furthermore, the study was conducted in the pediatric population and health centers
without advanced life support, making it difficult to generalize these results for
adult patients admitted to intensive care units.
The morbid effects of fluid overload in the various organs may be responsible for the
association between mortality and FB+. However, another aspect that could also
contribute to higher mortality in patients with fluid overload is reduced plasma
concentrations of hydrophilic antibiotics by increasing the volume of their
distribution.5555 Eyler RF, Mueller BA; Medscape. Antibiotic dosing in critically ill
patients with acute kidney injury. Nat Rev Nephrol 2011;7:226-35. DOI:
http://dx.doi.org/10.1038/nrneph.2011.12
http://dx.doi.org/10.1038/nrneph.2011.12...
As will be discussed below
in the topic, it is known that inflamed/septic patients develop endothelial damage
with increased capillary permeability predisposing to fluid shifts from the
intravascular compartment to the interstitium. Hydrophilic antibiotics such as
aminoglycosides, beta-lactam and glycopeptides may follow this fluid diversion,
resulting in subtherapeutic plasma concentrations.5555 Eyler RF, Mueller BA; Medscape. Antibiotic dosing in critically ill
patients with acute kidney injury. Nat Rev Nephrol 2011;7:226-35. DOI:
http://dx.doi.org/10.1038/nrneph.2011.12
http://dx.doi.org/10.1038/nrneph.2011.12...
Thus, the complex association between FB+ and mortality has not been
clearly elucidated. FB+ would be a severity marker of cardio/kidney/microvascular
severity or is it an independent factor for higher mortality in critically ill
patients? (Figure 1).
Positive fluid balance and AKI diagnosis: does FB+ interfere with the AKI diagnosis?
Currently, AKI diagnosis is based on the RIFLE criteria (Risk, Injury, Failure, Loss,
End stage Kidney Disease), AKIN (Acute Kidney Injury Network) and KDIGO (Kidney
Disease Improving Global Outcomes), which are based on serum creatinine increase and
reductions in urinary volume.5656 Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis
Quality Initiative workgroup. 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. Crit Care 2004;8:R204-12.,5757 Lassnigg A, Schmid ER, Hiesmayr M, Falk C, Druml W, Bauer P, et al.
Impact of minimal increases in serum creatinine on outcome in patients after
cardiothoracic surgery: do we have to revise current definitions of acute renal
failure? Crit Care Med 2008;36:1129-37. DOI:
http://dx.doi.org/10.1097/CCM.0b013e318169181a
http://dx.doi.org/10.1097/CCM.0b013e3181...
These criteria
were constructed from the observation that small increases in serum creatinine5757 Lassnigg A, Schmid ER, Hiesmayr M, Falk C, Druml W, Bauer P, et al.
Impact of minimal increases in serum creatinine on outcome in patients after
cardiothoracic surgery: do we have to revise current definitions of acute renal
failure? Crit Care Med 2008;36:1129-37. DOI:
http://dx.doi.org/10.1097/CCM.0b013e318169181a
http://dx.doi.org/10.1097/CCM.0b013e3181...
and diuresis reductions5858 Avila MO, Zanetta DM, Abdulkader RC, Yu L, Burdmann EA. Urine volume in
acute kidney injury: how much is enough? Ren Fail 2009;31:884-90. imply a worse prognosis for patients. The three classification
systems are divided into severity stages and there is growing evidence of a
correlation between the AKI stage by RIFLE and AKIN criteria and mortality.5959 Ricci Z, Cruz D, Ronco C. The RIFLE criteria and mortality in acute
kidney injury: A systematic review. Kidney Int 2008;73:538-46. DOI:
http://dx.doi.org/10.1038/sj.ki.5002743
http://dx.doi.org/10.1038/sj.ki.5002743...
Fluid balance was not included in the
diagnosis of AKI by any of these currently adopted criteria, a fact which leads us to
reflect on renal physiology.
It is known that a patient with normal renal function and usual diet (generating 800
mOsm of excreta per day) is able to eliminate up to 16 liters of maximally dilute
urine (50 mOsm/L), for physiological suppression of antidiuretic hormone (ADH).6060 Bichet DG. Urine Output in Diabetes Insipidus. In: Sterns RH, Forman JP,
eds. Up to Date; 2013 [Acessed May 18 2014]. Available from:
http://www.uptodate.com/contents/urine-output-in-diabetes-insipidus?source=search_result&search=Urine+Output+in+Diabetes+Insipidus.&selectedTitle=1%7E150
http://www.uptodate.com/contents/urine-o...
In turn, when a critically ill patient
develops AKI diagnosed by standard criteria and receives large fluid infusions
(antibiotics, sedation, vasoactive drugs etc.), it is easy to understand why he
develops FB+, since there is obvious impairment in their ability to excrete the
sodium overload received. However, critically ill patients without a diagnosis of AKF
by the RIFLE, AKIN or KDIGO criteria also evolve with positive FB. Why they could not
adequately increase the excretion of free salt and water, in response to sodium
overload?
There are medical conditions in the ICU that may predispose FB+, even in patients
without AKI. Hypotension, low cardiac output, vasodilation of sepsis (albeit without
hypotension), hypoalbuminemia, mechanical ventilation (MV) are able to activate the
neuroendocrine system (antidiuretic hormone, sympathetic nervous system,
renin-angiotensin-aldosterone system), with tubular retention of free water and
sodium.1212 Schrier R. Fluid administration in critically ill patients with acute
kidney injury. Clin J Am Soc Nephrol 2010;5:733-9. DOI:
http://dx.doi.org/10.2215/CJN.00060110
http://dx.doi.org/10.2215/CJN.00060110...
,1313 Townsend DR, Bagshaw SM. New insights on intravenous fluids, diuretics
and acute kidney injury. Nephron Clin Pract 2008;109:c206-16. PMID: 18802369 DOI:
http://dx.doi.org/10.1159/000142930
http://dx.doi.org/10.1159/000142930...
Because these patients usually receive large infusions of
water and salt, the result is positive FB and edema. MV with positive pressure can
also reduce lymphatic drainage, contributing to edema formation.1212 Schrier R. Fluid administration in critically ill patients with acute
kidney injury. Clin J Am Soc Nephrol 2010;5:733-9. DOI:
http://dx.doi.org/10.2215/CJN.00060110
http://dx.doi.org/10.2215/CJN.00060110...
13 Townsend DR, Bagshaw SM. New insights on intravenous fluids, diuretics
and acute kidney injury. Nephron Clin Pract 2008;109:c206-16. PMID: 18802369 DOI:
http://dx.doi.org/10.1159/000142930
http://dx.doi.org/10.1159/000142930...
-1414 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al.
Early goal-directed therapy in the treatment of severe sepsis and septic shock. N
Engl J Med 2001;345:1368-77. DOI:
http://dx.doi.org/10.1056/NEJMoa010307
http://dx.doi.org/10.1056/NEJMoa010307...
,2525 Bouchard J, Mehta RL. Fluid accumulation and acute kidney injury:
consequence or cause. Curr Opin Crit Care 2009;15:509-13. DOI:
http://dx.doi.org/10.1097/MCC.0b013e328332f653
http://dx.doi.org/10.1097/MCC.0b013e3283...
Other pathophysiological mechanisms that mediated the development of FB+ in
critically ill patients without a diagnosis of AKI by current criteria, possibly
involve two molecular systems: the angiopoietin/Tie (Ang/Tie)6161 van Meurs M, Kümpers P, Ligtenberg JJ, Meertens JH, Molema G, Zijlstra
JG. Bench-to-bedside review: Angiopoietin signalling in critical illness - a future
target? Crit Care 2009;13:207. DOI: http://dx.doi.org/10.1186/cc7153
http://dx.doi.org/10.1186/cc7153...
,6262 van der Heijden M, Pickkers P, van Nieuw Amerongen GP, van Hinsbergh VW,
Bouw MP, van der Hoeven JG, et al. Circulating angiopoietin-2 levels in the course of
septic shock: relation with fluid balance, pulmonary dysfunction and mortality.
Intensive Care Med 2009;35:1567-74. DOI:
http://dx.doi.org/10.1007/s00134-009-1560-y
http://dx.doi.org/10.1007/s00134-009-156...
system
and the endothelial glycocalyx.6363 De Backer D, Donadello K, Taccone FS, Ospina-Tascon G, Salgado D,
Vincent JL. Microcirculatory alterations: potential mechanisms and implications for
therapy. Ann Intensive Care 2011;1:27. DOI:
http://dx.doi.org/10.1186/2110-5820-1-27
http://dx.doi.org/10.1186/2110-5820-1-27...
,6464 Mulivor AW, Lipowsky HH. Inflammation- and ischemia-induced shedding of
venular glycocalyx. Am J Physiol Heart Circ Physiol 2004;286:H1672-80. PMID: 14704229
DOI: http://dx.doi.org/10.1152/ajpheart.00832.2003
http://dx.doi.org/10.1152/ajpheart.00832...
The
angiopoietin/Tie (Ang/Tie) system participates in major endothelial functions:
angiogenesis, fluid homeostasis maintenance, electrolytes and protein transport by
endothelial cells and inflammation/coagulation triggered by endothelial injury. These
three endothelial functions are altered in multiple organ dysfunction syndrome
(MODS): blood flow regulation is changed, vascular permeability becomes higher with
fluid and cell extravasation into the surrounding tissues and the mechanisms of
inflammation and coagulation are activated. Experimental and clinical studies suggest
that the Ang/Tie system participates in the vascular barrier dysfunction observed in
critically ill patients.6161 van Meurs M, Kümpers P, Ligtenberg JJ, Meertens JH, Molema G, Zijlstra
JG. Bench-to-bedside review: Angiopoietin signalling in critical illness - a future
target? Crit Care 2009;13:207. DOI: http://dx.doi.org/10.1186/cc7153
http://dx.doi.org/10.1186/cc7153...
,6262 van der Heijden M, Pickkers P, van Nieuw Amerongen GP, van Hinsbergh VW,
Bouw MP, van der Hoeven JG, et al. Circulating angiopoietin-2 levels in the course of
septic shock: relation with fluid balance, pulmonary dysfunction and mortality.
Intensive Care Med 2009;35:1567-74. DOI:
http://dx.doi.org/10.1007/s00134-009-1560-y
http://dx.doi.org/10.1007/s00134-009-156...
Angiopoietin 1 (Ang-1), a glycoprotein
produced by pericytes causes vascular stability by binding to the transmembrane Tie-2
receptor of endothelial cells. Rather, angiopoietin 2 (Ang-2) released by the
Weibel-Palade corpuscles of endothelial cell cytoplasm by inflammatory stimuli,
antagonizes the stabilizing effect of Ang-1 by binding competitively to the same
receptor Tie-2, weakening the intercellular junctions, predisposing to fluid leakage,
inflammation and coagulation. Patients with septic shock have high plasma levels of
Ang-2, that correlate with FB+, pulmonary dysfunction and mortality.6262 van der Heijden M, Pickkers P, van Nieuw Amerongen GP, van Hinsbergh VW,
Bouw MP, van der Hoeven JG, et al. Circulating angiopoietin-2 levels in the course of
septic shock: relation with fluid balance, pulmonary dysfunction and mortality.
Intensive Care Med 2009;35:1567-74. DOI:
http://dx.doi.org/10.1007/s00134-009-1560-y
http://dx.doi.org/10.1007/s00134-009-156...
It is also possible that the endothelial glycocalyx is reduced in situations of
ischemia and/or inflammation, such as sepsis or systemic inflammatory response
syndrome (SIRS).6363 De Backer D, Donadello K, Taccone FS, Ospina-Tascon G, Salgado D,
Vincent JL. Microcirculatory alterations: potential mechanisms and implications for
therapy. Ann Intensive Care 2011;1:27. DOI:
http://dx.doi.org/10.1186/2110-5820-1-27
http://dx.doi.org/10.1186/2110-5820-1-27...
Glycocalyx is a structure
composed of glycosaminoglycans and proteoglycans, which covers the endothelial
surface facing the capillary lumen, forming a barrier against the passage of
macromolecules and limiting the adhesion of inflammatory cells. The reduction of its
thickness, in situations of ischemia/inflammation, causes an increase in vascular
permeability and leukocyte adhesion, contributing to leakage of fluid and
macromolecules to the interstitium.6363 De Backer D, Donadello K, Taccone FS, Ospina-Tascon G, Salgado D,
Vincent JL. Microcirculatory alterations: potential mechanisms and implications for
therapy. Ann Intensive Care 2011;1:27. DOI:
http://dx.doi.org/10.1186/2110-5820-1-27
http://dx.doi.org/10.1186/2110-5820-1-27...
,6464 Mulivor AW, Lipowsky HH. Inflammation- and ischemia-induced shedding of
venular glycocalyx. Am J Physiol Heart Circ Physiol 2004;286:H1672-80. PMID: 14704229
DOI: http://dx.doi.org/10.1152/ajpheart.00832.2003
http://dx.doi.org/10.1152/ajpheart.00832...
Therefore,
ischemic and inflammatory attacks, so frequent in critically ill patients cause
endothelial dysfunction mediated by changes in the angiopoietin 2/Tie-2 system and
endothelial glycocalyx stripping, contributing to the diversion of fluid and
macromolecules from the intravascular compartment to the interstitium and, again,
activating the neuroendocrine system to retain fluids.6363 De Backer D, Donadello K, Taccone FS, Ospina-Tascon G, Salgado D,
Vincent JL. Microcirculatory alterations: potential mechanisms and implications for
therapy. Ann Intensive Care 2011;1:27. DOI:
http://dx.doi.org/10.1186/2110-5820-1-27
http://dx.doi.org/10.1186/2110-5820-1-27...
,6464 Mulivor AW, Lipowsky HH. Inflammation- and ischemia-induced shedding of
venular glycocalyx. Am J Physiol Heart Circ Physiol 2004;286:H1672-80. PMID: 14704229
DOI: http://dx.doi.org/10.1152/ajpheart.00832.2003
http://dx.doi.org/10.1152/ajpheart.00832...
On the other hand, critically ill patients may develop early and subtle AKI alone or
together with events described above, manifested by the inability to properly control
the fluid and sodium balance. The ability to concentrate and dilute urine depends on
the functional integrity of the renal medullary microcirculation and may be impaired
in the very early stages of kidney disease. While the cortical microcirculation is
able to make its self-regulation through changes in tone of afferent and efferent
arterioles up to certain limits for mean arterial pressure (MAP), the medullary
microcirculation seems to be more dependent on MAP and renal perfusion pressure, more
susceptible to ischemia and endothelial dysfunction in circulatory shock.6565 Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational
approach to perioperative fluid management. Anesthesiology 2008;109:723-40. PMID:
18813052 DOI: http://dx.doi.org/10.1097/ALN.0b013e3181863117
http://dx.doi.org/10.1097/ALN.0b013e3181...
Thus, positive FB can potentially be an AKI
biomarker, preceding the elevation of creatinine or decreased urine output. Moreover,
fluid overload can cause hemodilution and underestimate the level of serum
creatinine, delaying AKI diagnosis by the usual criteria.1818 Macedo E, Bouchard J, Soroko SH, Chertow GM, Himmelfarb J, Ikizler TA,
et al. Fluid accumulation, recognition and staging of acute kidney injury in
critically-ill patients. Crit Care 2010;14:R82. DOI:
http://dx.doi.org/10.1186/cc9004
http://dx.doi.org/10.1186/cc9004...
By analyzing data from the PICARD study, Macedo et
al., proposed using the following formula to adjust serum creatinine for
FB+:
The use of creatinine adjusted for this "correction factor" enabled the anticipation
of the AKI diagnosis, in at least one day.1818 Macedo E, Bouchard J, Soroko SH, Chertow GM, Himmelfarb J, Ikizler TA,
et al. Fluid accumulation, recognition and staging of acute kidney injury in
critically-ill patients. Crit Care 2010;14:R82. DOI:
http://dx.doi.org/10.1186/cc9004
http://dx.doi.org/10.1186/cc9004...
This set of facts suggests that it is necessary to consider the possible inclusion of
FB+ as an AKI criterion besides creatinine and urinary volume. Three observational
studies, a retrospective with 90 patients,6666 Dass B, Shimada M, Kambhampati G, Ejaz NI, Arif AA, Ejaz AA. Fluid
balance as an early indicator of acute kidney injury in CV surgery. Clin Nephrol
2012;77:438-44. PMID: 22595385 DOI:
http://dx.doi.org/10.5414/CN107278
http://dx.doi.org/10.5414/CN107278...
another prospective with 100 patient6767 Kambhampati G, Ross EA, Alsabbagh MM, Asmar A, Pakkivenkata U, Ejaz NI,
et al. Perioperative fluid balance and acute kidney injury. Clin Exp Nephrol
2012;16:730-8. DOI: http://dx.doi.org/10.1007/s10157-012-0623-5
http://dx.doi.org/10.1007/s10157-012-062...
and the
last: a secondary analysis of a prospective study involving 98 children suggested
that FB+ is an early marker of renal dysfunction. All studies evaluated patients
undergoing cardiovascular surgery6565 Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational
approach to perioperative fluid management. Anesthesiology 2008;109:723-40. PMID:
18813052 DOI: http://dx.doi.org/10.1097/ALN.0b013e3181863117
http://dx.doi.org/10.1097/ALN.0b013e3181...
,6666 Dass B, Shimada M, Kambhampati G, Ejaz NI, Arif AA, Ejaz AA. Fluid
balance as an early indicator of acute kidney injury in CV surgery. Clin Nephrol
2012;77:438-44. PMID: 22595385 DOI:
http://dx.doi.org/10.5414/CN107278
http://dx.doi.org/10.5414/CN107278...
Dass et
al.6666 Dass B, Shimada M, Kambhampati G, Ejaz NI, Arif AA, Ejaz AA. Fluid
balance as an early indicator of acute kidney injury in CV surgery. Clin Nephrol
2012;77:438-44. PMID: 22595385 DOI:
http://dx.doi.org/10.5414/CN107278
http://dx.doi.org/10.5414/CN107278...
conducted a post-hoc
analysis of the Nesiritide Study, a randomized placebo-controlled clinical trial,
from a single center, a study designed to assess the impact of prophylactic use of
nesiritide in patients requiring renal support therapy and/or in the mortality of
patients undergoing cardiovascular surgery. These authors investigated the hypothesis
that FB+ in the first 24 hours after cardiac surgery could be an indicator of
postoperative AKI. In this study, the incidence of AKI in patients with a median FB
greater than +849 ml/24 hours was 80%, versus 25% in those patients
with a median FB -1221 ml/24 hours (p = 0.001).
In a prospective observational study, Kambhampati et al.6767 Kambhampati G, Ross EA, Alsabbagh MM, Asmar A, Pakkivenkata U, Ejaz NI,
et al. Perioperative fluid balance and acute kidney injury. Clin Exp Nephrol
2012;16:730-8. DOI: http://dx.doi.org/10.1007/s10157-012-0623-5
http://dx.doi.org/10.1007/s10157-012-062...
divided the groups into FB quartiles, from the
intraoperative up to 48 hours postoperatively. AKI incidence in the 4th
quartile (FB+ median of 5000 ml/24 hours) was 52%, compared with a 16% incidence of
AKI in the 1st quartile (FB+ median of 500 ml/24 h), p =
0.016. Multivariate analysis adjusted for confounding variables such as age,
diabetes, hypertension, cardiopulmonary bypass time greater than 200 min, type of
surgery and rate of basal glomerular filtration revealed that the higher FB+ quartile
(4th quartile) was associated with a significantly higher risk of AKI
(OR 4.89; 95% CI; 1.38 to 24.1, p = 0.046).6767 Kambhampati G, Ross EA, Alsabbagh MM, Asmar A, Pakkivenkata U, Ejaz NI,
et al. Perioperative fluid balance and acute kidney injury. Clin Exp Nephrol
2012;16:730-8. DOI: http://dx.doi.org/10.1007/s10157-012-0623-5
http://dx.doi.org/10.1007/s10157-012-062...
The third and most recent study evaluated whether fluid overload in the early
postoperative period of cardiac surgery in 98 children would be associated with
higher morbidity, including increased incidence of AKI.6868 Hassinger AB, Wald EL, Goodman DM. Early postoperative fluid overload
precedes acute kidney injury and is associated with higher morbidity in pediatric
cardiac surgery patients. Pediatr Crit Care Med 2014;15:131-8. DOI:
http://dx.doi.org/10.1097/PCC.0000000000000043
http://dx.doi.org/10.1097/PCC.0000000000...
Early postoperative fluid overload was defined as FB+ greater
than 5% of baseline weight, from the immediate postoperative period in the ICU until
the first postoperative day. Fifty percent of children with fluid overload upon ICU
admission developed AKI in the first postoperative day, whereas only 14.4% of those
who did not have early fluid overload developed AKI (p = 0.023).
Fluid overload preceded the onset of AKI, which occurred in any postoperative day. 8%
fluid overload (equivalent to 80 ml/kg) showed a specificity of 90% for the
subsequent development of AKI RIFLE I or F. Fluid overload was also associated with a
longer hospital stay (3.5 days more), two more days under inotropes, and higher
prevalence of prolonged MV.6868 Hassinger AB, Wald EL, Goodman DM. Early postoperative fluid overload
precedes acute kidney injury and is associated with higher morbidity in pediatric
cardiac surgery patients. Pediatr Crit Care Med 2014;15:131-8. DOI:
http://dx.doi.org/10.1097/PCC.0000000000000043
http://dx.doi.org/10.1097/PCC.0000000000...
To date, there
is no available evidence testing the hypothesis that FB+ is an early marker of AKI,
also in non-surgical patients.
Abstract
Early volume expansion guided by the optimization parameters of microcirculatory perfusion remains a recommendation to reduce the incidence of AKI 'and minimizes mortality in septic patients. Volume expansion is also a preventive measure for nephrotoxic AKI, as in the iodine contrast-induced AKI, to aminoglycosides, amphotericin B, rhabdomyolysis and tumor lysis syndrome, among other situations. In turn, the maintenance of ad libitum fluid infusion in critically ill patients with or without acute kidney failure, can lead to accumulated FB+ and increase morbidity and mortality. FB+ can also delay AKI diagnosis, by serum creatinine hemodilution.
FB+ could be a manifestation of the inability to adequately control fluid and salt balance in critically ill and inflamed patients by changes in the kidney medullary microcirculation function integrity.
In conclusion, FB+ may be an early AKI biomarker and an independent risk factor for mortality in ICU patients. Randomized clinical trials are needed to evaluate the complex interrelationship between FB+, AKI and death.
Referências
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Publication Dates
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Publication in this collection
Jul-Sep 2014
History
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Received
12 Feb 2014 -
Accepted
01 Mar 2014