Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis

Zou, Yan; Ma, Ke; Xiong, Ji-Bin; Xi, Cai-Hua; Deng, Xiao-Jun

doi:10.1590/1516-3180.2017.0285281017

Yan Zou

MD. Associate Professor, Department of Intensive Care Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.

http://orcid.org/0000-0002-6129-1329

Ke Ma

MD. Associate Professor, Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.

http://orcid.org/0000-0003-0871-0819

Ji-Bin Xiong

MD. Assistant Professor, Department of Hyperbaric Oxygen Therapy, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.

http://orcid.org/0000-0002-7983-9452

Cai-Hua Xi

MD. Associate Professor, Department of Intensive Care Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.

Xiao-Jun Deng

MD. Associate Professor, Department of Intensive Care Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.

Address for correspondence: Ke Ma Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital East Campus, No. 222 Huanhuxisan Road, Shanghai 201306 - China Tel. +86 18930177703 Fax. +862138297733 E-mail: dockema@163.com

Conflict of interest: None

Figures (7)
Tables (5)

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Figure 1.
Publication bias was evaluated using a funnel plot.

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Figure 2.
Flow chart of study selection.

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Figure 3.
All-cause mortality ascertained at final follow-up, after use of albumin, compared with crystalloid.

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Figure 4.
All-cause mortality ascertained at different follow-ups, after use of albumin, compared with crystalloid.

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Figure 5.
A diversity-adjusted information size of 4,815 patients was calculated using α = 0.05 (two-sided), β = 0.20 (power 80%), D2 = 0%, an anticipated relative risk of 10.0% (refer to our meta-analysis) and an event proportion of 39% in the control arm (refer to our meta-analysis). The cumulative z curve was constructed using a random-effects model. Trial sequential analysis showed that 3,088 patients out of the required information size of 4,815 patients were accrued. The cumulative z curve touched the conventional boundary for benefit but did not cross the trial sequential monitoring boundary for benefit.

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Figure 6.
All-cause mortality ascertained at final follow-up, after use of different albumin concentrations, compared with crystalloid.

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Figure 7.
A diversity-adjusted information size of 3,177 patients was calculated using α = 0.05 (two-sided), β = 0.20 (power 80%), D2 = 0%, an anticipated relative risk of 12.0% (refer to our meta-analysis) and an event proportion of 40.2% in the control arm (refer to our meta-analysis). The cumulative z curve was constructed using a random-effects model. Trial sequential analysis showed that 1,913 patients out of the required information size of 3,177 patients were accrued. The cumulative z curve touched the conventional boundary for benefit but did not cross the trial sequential monitoring boundary for benefit.

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Table 1.
Search strategies used in MEDLINE, Embase and Cochrane databases

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Table 2.
Quality evaluation on the studies included

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Table 3.
Quality-of-evidence summary table according to GRADE

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Table 4.
Characteristics of studies included

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First author Subject Reason for exclusion Dahn 19791 Negative inotropic effect of albumin resuscitation for shock. Seriously injured patients were included in the study, and data on severe sepsis were inadequate. Lucas 19792 Impaired salt and water excretion after albumin resuscitation for hypovolemic shock. Hypovolemic shock patients were included in the study, and data on severe sepsis were inadequate. Lucas 19803 Impaired pulmonary function after albumin resuscitation from shock. Shock patients were included in the study, and data on severe sepsis were inadequate. Brown 19884 Effect of albumin supplementation during parenteral nutrition on hospital morbidity. Patients requiring central total parenteral nutrition were included in the study, and data on severe sepsis were inadequate. Foley 19905 Albumin supplementation in critically ill patients. Hypoalbuminemic patients were included in the study, and data on severe sepsis were inadequate. Younes 19926 Hypertonic solutions for treating hypovolemic shock: a prospective, randomized study on patients admitted to the emergency room. Hypovolemic shock patients were included in the study, and data on severe sepsis were inadequate. Stockwell 19927 Colloid solutions in critically ill patients: a randomized comparison of albumin and polygeline. Outcome and duration of stay in the intensive care unit. All patients were included in the study, and data on severe sepsis were inadequate. Tuchschmidt 19928 Elevation of cardiac output and oxygen delivery for improvement of outcomes in septic shock cases. Septic shock patients were treated using an algorithm to increase confidence intervals to a different level. Golub 19949 Efficacy of albumin supplementation in surgical intensive care unit: a prospective, randomized study. The study was conducted in the surgical intensive care unit, and data on severe sepsis were inadequate. Steltzer 199410 Hemodynamic evaluation during small-volume resuscitation among patients with acute respiratory failure. Acute respiratory failure patients were included in the study, and data on severe sepsis were inadequate. Boldt 199611 Effects of albumin versus hydroxyethyl starch solution on cardio respiratory and circulatory variables in critically ill patients. Comparison was between albumin and low-molecular weight hydroxyethyl starch solution, not between albumin and crystalloid. Rock 199712 Pentastarch instead of albumin as replacement fluid for therapeutic plasma exchange. Comparison was between albumin and pentastarch, not between albumin and crystalloid. Rubin 199713 Randomized, double blind study on intravenous human albumin in hypoalbuminemic patients receiving total parenteral nutrition. Hypoalbuminemic patients were included in the study, and data on severe sepsis were inadequate. Ernest 199914 Distribution of normal saline and 5% albumin infusions among septic patients. Septic patients were included in the study, and data on severe sepsis were inadequate. Wu 200115 Hemodynamic response of modified fluid gelatin compared with lactated Ringer’s solution for volume expansion in emergency resuscitation of hypovolemic shock patients: preliminary report on a prospective, randomized trial. Hypovolemic shock patients were included in the study, and data on severe sepsis were inadequate. Oliveira 200216 Acute hemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis. Comparison was between hypertonic saline/dextran solution and saline, not between albumin and crystalloid. Quinlan 200417 Albumin influenced total plasma antioxidant capacity favorably in patients with acute lung injury. Acute lung injury patients were included in the study, and data on severe sepsis were inadequate. Veneman 200418 Human albumin and starch administration in critically ill patients: a prospective randomized clinical trial. Severe sepsis patients were included in the study, and the mortality data on the albumin group and crystalloid group were inadequate. Vincent 200519 Albumin administration in acutely ill patients in relation to increased mortality :results from the SOAP study. Not a randomized controlled or parallel clinical trial. Palumbo 200620 Effects of hydroxyethyl starch solution on critically ill patients. Comparison was between albumin and hydroxyethyl starch, not between albumin and crystalloid. Dubois 200612 Albumin administration improved organ function in critically ill hypoalbuminemic patients: a prospective, randomized, controlled, pilot study. Hypoalbuminemic patients were included in the study, and data on severe sepsis were inadequate. Bellomo 200622 Effects of saline or albumin resuscitation on acid-base status and serum electrolytes. Not a randomized controlled or parallel clinical trial. McIntyre 200723 Resuscitating patients with early severe sepsis: a Canadian multicenter observational study. Not a randomized controlled or parallel clinical trial. Guidet 200724 The COASST study: cost-effectiveness of albumin in cases of severe sepsis and septic shock. Not a randomized controlled or parallel clinical trial. McIntyre 200825 Fluid resuscitation in management of early septic shock (FINESS): a randomized controlled feasibility trial. Comparison was between pentastarch and saline, not between albumin and crystalloid. Friedman 200826 Hemodynamic effects of 6% and 10% hydroxyethyl starch solutions versus 4% albumin solution in septic patients. Comparison was between hydroxyethyl starch and albumin, not between albumin and crystalloid. Schortgen 200827 Risk associated with hyperoncotic colloids in patients with shock. Not a randomized controlled or parallel clinical trial. Dolecek 200928 Therapeutic influence of 20% albumin versus 6% hydroxyethyl starch on extravascular lung water in septic patients: a randomized controlled trial. Comparison was between hydroxyethyl starch and albumin, not between albumin and crystalloid. Bellomo 200929 Effects of saline or albumin resuscitation on standard coagulation tests. Not a randomized controlled or parallel clinical trial. van der Heijden 200930 Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and non-septic critically ill patients with hypovolemia. Hypovolemic septic patients were included in the study, and the mortality data on the albumin group and crystalloid group were inadequate. Trof 201031 Greater cardiac response of colloid than saline fluid loading in septic and non-septic critically ill patients with clinical hypovolemia. Critically ill septic patients were included in the study, and the mortality data on the albumin group and crystalloid group were inadequate. Finfer 201032 Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Not a randomized controlled or parallel clinical trial. Zhu 201133 Hypertonic saline and hydroxyethyl starch for treating severe sepsis. Comparison was between hypertonic saline and hydroxyethyl starch, not between albumin and crystalloid. Crystalloid versus Hydroxyethyl Starch Trial (CHEST) Management Committee 201134 Crystalloid versus hydroxyethyl starch trial: protocol for a multicenter randomized controlled trial on fluid resuscitation with 6% hydroxyl starch (130/0.4) compared with 0.9% sodium chloride (saline) in intensive care patients, regarding mortality. Comparison was between crystalloid and hydroxyethyl starch, not between albumin and crystalloid. Scandinavian Critical Care Trials Group 201135 Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S: Scandinavian Starch for Severe Sepsis/Septic Shock trial): study protocol, design and rationale for a double-blinded, randomized clinical trial. Comparison was between crystalloid and hydroxyethyl starch, not between albumin and crystalloid. McIntyre 201236 Fluid resuscitation with 5% albumin versus normal saline in early septic shock: a pilot randomized, controlled trial. Septic shock patients were included in the study, and the mortality data on the albumin group and saline group were inadequate. van Haren 201237 Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study. Comparison was between hypertonic fluid and isotonic fluid, not between albumin and crystalloid. Myburgh 201238 Hydroxyethyl starch or saline for fluid resuscitation in intensive care. Comparison was between hydroxyethyl starch and saline, not between albumin and crystalloid. Yunos 201239 Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. Not a randomized controlled or parallel clinical trial McIntyre 201240 The PRECISE RCT: evolution of an early septic shock fluid resuscitation trial. Septic shock patients were included in the study, and the mortality data on the albumin group and saline group were inadequate. Perez 201341 Intravenous 0.9% sodium chloride therapy did not reduce length of stay of alcohol-intoxicated patients in the emergency department: a randomized controlled trial. Acute alcohol intoxication patients were included in the study; the mortality data on the albumin group and saline group were inadequate; and the comparison was not between albumin and crystalloid. Masson 201442 Presepsin (soluble CD14 subtype) and procalciton in levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial. Comparison was not between albumin and crystalloid. Caironi 201543 Albumin in critically ill patients: the ideal colloid? Not a controlled or parallel clinical trial. Chang 201644 Choice of fluid therapy in the initial management of sepsis, severe sepsis, and septic shock. Choice of fluid therapy in the initial management of sepsis, severe sepsis, and septic shock.

Databases	Search strategy
MEDLINE(via PubMed)	((((“Sepsis”[Mesh]) OR (((((((sepsis[Title/Abstract]) OR septic [Title/Abstract]) OR Pyemia[Title/Abstract]) OR Pyohemia [Title/Abstract]) OR Pyaemia[Title/Abstract]) OR Septicemia [Title/Abstract]) OR Blood Poisoning[Title/Abstract]))) AND ((“Albumins”[Mesh]) OR albumin[Title/Abstract])) AND (((“Mortality”[Mesh]) OR “Survival”[Mesh]) OR ((((((mortality [Title/Abstract]) OR fatality[Title/Abstract]) OR survival[Title/Abstract]) OR death[Title/Abstract]) OR prognos[Title/Abstract]) OR predict*[Title/Abstract]))
EMBASE	(‘sepsis’/exp OR ( (Sepsis OR septic OR Pyemia* OR Pyohemia* OR Pyaemia* OR SepticemiaOR ‘Blood Poisoning’ ):ab,ti ) ) AND (‘albumin’/exp OR albumin:ab,ti) AND (((mortality OR fatality OR death OR prognos* OR predict* OR survival) :ab,ti) or ‘mortality’/exp)
Cochrane Central Register of Controlled Trials	([Sepsis] or (sepsis:ti,ab,kw or sepic:ti,ab,kw or Pyemia:ti,ab,kw or Pyohemia:ti,ab,kw or Pyaemia:ti,ab,kw) or (Septicemia:ti,ab,kw or Blood Poisoning:ti,ab,kw)) and ([Albumins] or albumin: ti,ab, kw ) and ([Mortality] or [Survival] or mortality:ti,ab,kw or survival:ti,ab,kw or fatality:ti,ab,kw or death:ti,ab,kw or prognos :ti,ab,kw or predict*:ti,ab,kw)

Study name	Sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias	Overall risk of bias
Rackow et al.¹⁹19. Rackow EC, Falk JL, Fein IA, et al. Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock. Crit Care Med. 1983;11(11):839-50. PMID: 6194934.	unclear	unclear	high risk	low risk	low risk	low risk	unclear	high risk
SAFE study²⁰20. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247-56. PMID: 15163774; doi: 10.1056/NEJMoa040232. https://doi.org/10.1056/NEJMoa040232...	low risk	low risk	low risk	low risk	low risk	low risk	unclear	unclear
EARSS study¹⁴14. Charpentier J, Mira JP, EARSS Study Group. Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study (Abstract). Intensive Care Med. 2011; 37(Suppl1):S115.	low risk	low risk	unclear	low risk	low risk	low risk	low risk	unclear
RASP study¹⁸18. Park C, Osawa E, Almeida J, et al. Lactated Ringer Versus Albumin in Early Sepsis Therapy (RASP) study: preliminary data of a randomized controlled trial. Crit Care. 2015;19(Suppl 1):P355. doi:10.1186/cc14435. https://doi.org/10.1186/cc14435...	low risk	low risk	low risk	low risk	low risk	low risk	unclear	unclear
CRYSTAL study²¹21. Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310(17):1809-17. PMID: 24108515; doi: 10.1001/jama.2013.280502. https://doi.org/10.1001/jama.2013.280502...	low risk	low risk	high risk	low risk	low risk	unclear	low risk	high risk
ALBIOS study¹⁵15. Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370(15):1412-21. PMID: 24635772; doi: 10.1056/NEJMoa1305727. https://doi.org/10.1056/NEJMoa1305727...	low risk	low risk	unclear	low risk	low risk	low risk	low risk	unclear

Quality assessment						No of patients			Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	All-cause mortality at final follow-up after use of albumin	Crystalloid	Relative risk (95% CI)	Absolute	Quality	Importance
All-cause mortality at final follow-up after use of albumin, compared with crystalloids
6	randomized trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	466/1282 (36.3%)	705/1806 (39%)	RR 0.91 (0.83 to 1)	35 fewer per 1,000 (from 66 fewer to 0 more)	Moderate	Critical
6	randomized trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none		44.6%	RR 0.91 (0.83 to 1)	40 fewer per 1,000 (from 76 fewer to 0 more)	Moderate	Critical
All-cause mortality at final follow-up after use of different albumin concentrations, compared with crystalloid - hyperoncotic (20% albumin)
2	randomized trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	339/957 (35.4%)	384/956 (40.2%)	RR 0.88 (0.79 to 0.99)	48 fewer per 1,000 (from 4 fewer to 84 fewer)	High	Critical
								38.1%		46 fewer per 1,000 (from 4 fewer to 80 fewer)
								35.4%		18 more per 1,000 (from 92 fewer to 177 more)
Effect of use of albumin versus crystalloid on all-cause mortality among patients with septic shock - subgroup assessed regarding mortality after 28 days (follow-up after 28 days)
4	randomized trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	215/717 (30%)	381/1239 (30.8%)	RR 0.96 (0.83 to 1.11)	12 fewer per 1,000 (from 52 fewer to 34 more)	Moderate	Critical
4	randomized trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none		33.7%	RR 0.96 (0.83 to 1.11)	13 fewer per 1,000 (from 57 fewer to 37 more)	Moderate	Critical
Effect of use of albumin versus crystalloid on all-cause mortality among patients with septic shock - mortality assessed after 90 days (follow-up after 90 days)
2	randomized trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	265/617 (42.9%)	478/1120 (42.7%)	RR 0.89 (0.79 to 1)	47 fewer per 1,000 (from 90 fewer to 0 more)	Moderate	Critical
2	randomized trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none		42.6%	RR 0.89 (0.79 to 1)	47 fewer per 1,000 (from 89 fewer to 0 more)	Moderate	Critical
All-cause mortality at final follow-up according to different risks of bias - All-cause mortality at final follow-up in subgroup with low or unclear risk of bias
4	randomized trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	439/1216 (36.1%)	505/1245 (40.6%)	RR 0.9 (0.82 to 0.99)	41 fewer per 1,000 (from 4 fewer to 73 fewer)	High	Critical
4	randomized trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none		44.6%	RR 0.9 (0.82 to 0.99)	45 fewer per 1,000 (from 4 fewer to 80 fewer)	High	Critical
All-cause mortality at final follow-up according to different risks of bias - All-cause mortality at final follow-up in subgroup with high risk of bias
2	no methodology chosen					none	27/66 (40.9%)	200/561 (35.7%)	RR 1.03 (0.75 to 1.42)	11 more per 1,000 (from 89 fewer to 150 more)	High	Critical
2	no methodology chosen					none		55.2%	RR 1.03 (0.75 to 1.42)	17 more per 1,000 (from 138 fewer to 232 more)	High	Critical

Study name	Year	Country	Centers	Albumin concentration	Type of crystalloid	28-day mortality (albumin group)	28-day mortality (crystalloid group)	90-day mortality (albumin group)	90-day mortality (crystalloid group)	Final follow-up (albumin group)	Final follow-up (crystalloid group)
Rackow et al.¹⁹19. Rackow EC, Falk JL, Fein IA, et al. Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock. Crit Care Med. 1983;11(11):839-50. PMID: 6194934.	1983	USA	1	5%	Normal saline	N/A*	N/A	N/A	N/A	5/7	3/4
SAFE study²⁰20. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247-56. PMID: 15163774; doi: 10.1056/NEJMoa040232. https://doi.org/10.1056/NEJMoa040232...	2004, 2011	Australia and New Zealand	16	4%	Normal saline	70/209	90/229	N/A	N/A	70/209	90/229
EARSS study¹⁴14. Charpentier J, Mira JP, EARSS Study Group. Efficacy and tolerance of hyperoncotic albumin administration in septic shock patients: the EARSS study (Abstract). Intensive Care Med. 2011; 37(Suppl1):S115.	2011	France	29	20%	Normal saline	96/399	103/393	N/A	N/A	96/399	103/393
CRYSTAL study²¹21. Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310(17):1809-17. PMID: 24108515; doi: 10.1001/jama.2013.280502. https://doi.org/10.1001/jama.2013.280502...	2013	France, Belgium, Canada, Algeria and Tunisia	57	5% or 20%	Normal saline	19/59	157/557	22/59	197/557	22/59	197/557
ALBIOS study¹⁵15. Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370(15):1412-21. PMID: 24635772; doi: 10.1056/NEJMoa1305727. https://doi.org/10.1056/NEJMoa1305727...	2014	Italy	100	20%	Crystalloid	N/A	N/A	243/558	281/563	243/558	281/563
RASP study¹⁸18. Park C, Osawa E, Almeida J, et al. Lactated Ringer Versus Albumin in Early Sepsis Therapy (RASP) study: preliminary data of a randomized controlled trial. Crit Care. 2015;19(Suppl 1):P355. doi:10.1186/cc14435. https://doi.org/10.1186/cc14435...	2015	Brazil	1	4%	Lactated Ringer	30/50**	31/60**	N/A	N/A	30/50	31/60

First author	Subject	Reason for exclusion
Dahn 1979¹	Negative inotropic effect of albumin resuscitation for shock.	Seriously injured patients were included in the study, and data on severe sepsis were inadequate.
Lucas 1979²	Impaired salt and water excretion after albumin resuscitation for hypovolemic shock.	Hypovolemic shock patients were included in the study, and data on severe sepsis were inadequate.
Lucas 1980³	Impaired pulmonary function after albumin resuscitation from shock.	Shock patients were included in the study, and data on severe sepsis were inadequate.
Brown 1988⁴	Effect of albumin supplementation during parenteral nutrition on hospital morbidity.	Patients requiring central total parenteral nutrition were included in the study, and data on severe sepsis were inadequate.
Foley 1990⁵	Albumin supplementation in critically ill patients.	Hypoalbuminemic patients were included in the study, and data on severe sepsis were inadequate.
Younes 1992⁶	Hypertonic solutions for treating hypovolemic shock: a prospective, randomized study on patients admitted to the emergency room.	Hypovolemic shock patients were included in the study, and data on severe sepsis were inadequate.
Stockwell 1992⁷	Colloid solutions in critically ill patients: a randomized comparison of albumin and polygeline. Outcome and duration of stay in the intensive care unit.	All patients were included in the study, and data on severe sepsis were inadequate.
Tuchschmidt 1992⁸	Elevation of cardiac output and oxygen delivery for improvement of outcomes in septic shock cases.	Septic shock patients were treated using an algorithm to increase confidence intervals to a different level.
Golub 1994⁹	Efficacy of albumin supplementation in surgical intensive care unit: a prospective, randomized study.	The study was conducted in the surgical intensive care unit, and data on severe sepsis were inadequate.
Steltzer 1994¹⁰	Hemodynamic evaluation during small-volume resuscitation among patients with acute respiratory failure.	Acute respiratory failure patients were included in the study, and data on severe sepsis were inadequate.
Boldt 1996¹¹	Effects of albumin versus hydroxyethyl starch solution on cardio respiratory and circulatory variables in critically ill patients.	Comparison was between albumin and low-molecular weight hydroxyethyl starch solution, not between albumin and crystalloid.
Rock 1997¹²	Pentastarch instead of albumin as replacement fluid for therapeutic plasma exchange.	Comparison was between albumin and pentastarch, not between albumin and crystalloid.
Rubin 1997¹³	Randomized, double blind study on intravenous human albumin in hypoalbuminemic patients receiving total parenteral nutrition.	Hypoalbuminemic patients were included in the study, and data on severe sepsis were inadequate.
Ernest 1999¹⁴	Distribution of normal saline and 5% albumin infusions among septic patients.	Septic patients were included in the study, and data on severe sepsis were inadequate.
Wu 2001¹⁵	Hemodynamic response of modified fluid gelatin compared with lactated Ringer’s solution for volume expansion in emergency resuscitation of hypovolemic shock patients: preliminary report on a prospective, randomized trial.	Hypovolemic shock patients were included in the study, and data on severe sepsis were inadequate.
Oliveira 2002¹⁶	Acute hemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis.	Comparison was between hypertonic saline/dextran solution and saline, not between albumin and crystalloid.
Quinlan 2004¹⁷	Albumin influenced total plasma antioxidant capacity favorably in patients with acute lung injury.	Acute lung injury patients were included in the study, and data on severe sepsis were inadequate.
Veneman 2004¹⁸	Human albumin and starch administration in critically ill patients: a prospective randomized clinical trial.	Severe sepsis patients were included in the study, and the mortality data on the albumin group and crystalloid group were inadequate.
Vincent 2005¹⁹	Albumin administration in acutely ill patients in relation to increased mortality :results from the SOAP study.	Not a randomized controlled or parallel clinical trial.
Palumbo 2006²⁰	Effects of hydroxyethyl starch solution on critically ill patients.	Comparison was between albumin and hydroxyethyl starch, not between albumin and crystalloid.
Dubois 2006¹²	Albumin administration improved organ function in critically ill hypoalbuminemic patients: a prospective, randomized, controlled, pilot study.	Hypoalbuminemic patients were included in the study, and data on severe sepsis were inadequate.
Bellomo 2006²²	Effects of saline or albumin resuscitation on acid-base status and serum electrolytes.	Not a randomized controlled or parallel clinical trial.
McIntyre 2007²³	Resuscitating patients with early severe sepsis: a Canadian multicenter observational study.	Not a randomized controlled or parallel clinical trial.
Guidet 2007²⁴	The COASST study: cost-effectiveness of albumin in cases of severe sepsis and septic shock.	Not a randomized controlled or parallel clinical trial.
McIntyre 2008²⁵	Fluid resuscitation in management of early septic shock (FINESS): a randomized controlled feasibility trial.	Comparison was between pentastarch and saline, not between albumin and crystalloid.
Friedman 2008²⁶	Hemodynamic effects of 6% and 10% hydroxyethyl starch solutions versus 4% albumin solution in septic patients.	Comparison was between hydroxyethyl starch and albumin, not between albumin and crystalloid.
Schortgen 2008²⁷	Risk associated with hyperoncotic colloids in patients with shock.	Not a randomized controlled or parallel clinical trial.
Dolecek 2009²⁸	Therapeutic influence of 20% albumin versus 6% hydroxyethyl starch on extravascular lung water in septic patients: a randomized controlled trial.	Comparison was between hydroxyethyl starch and albumin, not between albumin and crystalloid.
Bellomo 2009²⁹	Effects of saline or albumin resuscitation on standard coagulation tests.	Not a randomized controlled or parallel clinical trial.
van der Heijden 2009³⁰	Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and non-septic critically ill patients with hypovolemia.	Hypovolemic septic patients were included in the study, and the mortality data on the albumin group and crystalloid group were inadequate.
Trof 2010³¹	Greater cardiac response of colloid than saline fluid loading in septic and non-septic critically ill patients with clinical hypovolemia.	Critically ill septic patients were included in the study, and the mortality data on the albumin group and crystalloid group were inadequate.
Finfer 2010³²	Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units.	Not a randomized controlled or parallel clinical trial.
Zhu 2011³³	Hypertonic saline and hydroxyethyl starch for treating severe sepsis.	Comparison was between hypertonic saline and hydroxyethyl starch, not between albumin and crystalloid.
Crystalloid versus Hydroxyethyl Starch Trial (CHEST) Management Committee 2011³⁴	Crystalloid versus hydroxyethyl starch trial: protocol for a multicenter randomized controlled trial on fluid resuscitation with 6% hydroxyl starch (130/0.4) compared with 0.9% sodium chloride (saline) in intensive care patients, regarding mortality.	Comparison was between crystalloid and hydroxyethyl starch, not between albumin and crystalloid.
Scandinavian Critical Care Trials Group 2011³⁵	Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S: Scandinavian Starch for Severe Sepsis/Septic Shock trial): study protocol, design and rationale for a double-blinded, randomized clinical trial.	Comparison was between crystalloid and hydroxyethyl starch, not between albumin and crystalloid.
McIntyre 2012³⁶	Fluid resuscitation with 5% albumin versus normal saline in early septic shock: a pilot randomized, controlled trial.	Septic shock patients were included in the study, and the mortality data on the albumin group and saline group were inadequate.
van Haren 2012³⁷	Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study.	Comparison was between hypertonic fluid and isotonic fluid, not between albumin and crystalloid.
Myburgh 2012³⁸	Hydroxyethyl starch or saline for fluid resuscitation in intensive care.	Comparison was between hydroxyethyl starch and saline, not between albumin and crystalloid.
Yunos 2012³⁹	Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.	Not a randomized controlled or parallel clinical trial
McIntyre 2012⁴⁰	The PRECISE RCT: evolution of an early septic shock fluid resuscitation trial.	Septic shock patients were included in the study, and the mortality data on the albumin group and saline group were inadequate.
Perez 2013⁴¹	Intravenous 0.9% sodium chloride therapy did not reduce length of stay of alcohol-intoxicated patients in the emergency department: a randomized controlled trial.	Acute alcohol intoxication patients were included in the study; the mortality data on the albumin group and saline group were inadequate; and the comparison was not between albumin and crystalloid.
Masson 2014⁴²	Presepsin (soluble CD14 subtype) and procalciton in levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial.	Comparison was not between albumin and crystalloid.
Caironi 2015⁴³	Albumin in critically ill patients: the ideal colloid?	Not a controlled or parallel clinical trial.
Chang 2016⁴⁴	Choice of fluid therapy in the initial management of sepsis, severe sepsis, and septic shock.	Choice of fluid therapy in the initial management of sepsis, severe sepsis, and septic shock.

[1] Address for correspondence: Ke Ma Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital East Campus, No. 222 Huanhuxisan Road, Shanghai 201306 - China Tel. +86 18930177703 Fax. +862138297733 E-mail: dockema@163.com

Brasil

Brasil

Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis

ABSTRACT

BACKGROUND:

DESIGN AND SETTING:

METHODS:

RESULTS:

CONCLUSIONS: