Does a conservative ?uid management strategy in the perioperative management of lung resection patients reduce the risk of acute
lung injury?
Robert G.Evans a,b and Babu Naidu a,b,*
a Department of Thoracic Surgery,Heart of England NHS Foundation Trust,Birmingham,UK b
University of Warwick,Coventry,UK
*Corresponding author.Department of Thoracic Surgery,Heart of England NHS Foundation Trust,Bordesley Green East B95SS,UK.Tel:+44-121-4243561;fax:+44-1214240562;e-mail:babu.naidu@https://www.doczj.com/doc/9b13647866.html, (B.Naidu).
Received 6December 2011;received in revised form 23March 2012;accepted 1April 2012
Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol.The question addressed was whether a conser-vative ?uid management strategy in the perioperative management of lung resection patients is associated with a reduced incidence of postoperative acute lung injury (PALI)and/or acute respiratory distress syndrome (ARDS)in the recovery period.Sixty-seven papers were found using the reported search,of which 13level III and 1level IV evidence studies represented the best evidence to answer the question.Two retrospective case-control studies demonstrated a direct association between liberal ?uid intake and the incidence of PALI/ARDS following lung resection on multivariate analysis (MV A)with odds ratios (ORs)of 1.42(95%CI 1.09–4.32,P =0.011)and 2.91(1.9–7.4,P =0.001).In non-PALI/ARDS cases,the mean intraoperative ?uid infusion volume was signi ?cantly less [1.22l (1.17–1.26)vs 1.68l (1.46–1.9)P =0.005],the ?uid balance over the ?rst 24postoperative hours was signi ?cantly less [1.52l positive (1.44–1.60)vs 2.0l positive (1.6–2.4)P =0.026]and cumulated intra-and postoperative ?uid infusion was signi ?cantly less [2.0ml/kg/h (1.7–2.3)vs 2.6ml/kg/h (2.3–2.9)P =0.003].These data show that the difference between ?uid regimes associated with an increased incidence of PALI/ARDS (i.e.‘liberal ’)and those which are not (i.e.‘conservative ’)is narrow but signi ?cant.However,this does not prove a causative role for liberal ?uid in the multifactorial development of PALI/ARDS.On this best evidence,we recommend intra-and postoperative maintenance ?uid to be administered at 1–2ml/kg/h and that a positive ?uid balance of 1.5l should not be exceeded in the perioperative period with caution being exercised with regard to the adequacy of oxygen delivery.If the ?uid balance exceeds this threshold,a high index of suspicion for PALI/ARDS should be adopted and escalation of the level of care should be considered.If a patient develops signs of hypoperfusion after these thresholds are exceeded,inotropic/vasopressor support should be considered.
Keywords:Pneumonectomy ?Lung resection ?Postoperative acute lung injury (PALI)?Acute respiratory distress syndrome (ARDS)?Fluid balance
INTRODUCTION
A best evidence topic was constructed according to a structured protocol as described in ICVTS [1].
THREE-PART QUESTION
In [perioperative lung resection patients]is [a conservative ?uid management strategy]superior to [a liberal ?uid management strategy]in terms of [reduced incidence of postoperative acute lung injury/acute respiratory distress syndrome]?
CLINICAL SCENARIO
A 61-year old man underwent an open left lower lobectomy.He received 2.1l of intravenous crystalloid intraoperatively and in
the ?rst 24h postoperatively,he received ?uids at 125ml/h.He weighed 85kg.Eight hours postoperatively,his urine output was 10ml/h for two consecutive hours.His ?uid balance was 2.3l positive for the last 24h.You consider whether to administer a ?uid challenge or to commence vasopressor/inotropic support mindful of the risk of postoperative acute lung injury (PALI)/acute respiratory distress syndrome (ARDS).
SEARCH STRATEGY
MEDLINE was searched from 1950to October 2011,and EMBASE was searched from 1980to October 2011using the OVID interface.The search terms were:[acute lung injury.mp OR acute respiratory distress syndrome.mp OR pulmonary oedema.mp]AND [lung resection.mp OR pneumonectomy.mp OR lobec-tomy.mp]AND [intravenous ?uid.mp OR ?uid balance.mp].The Cochrane library was also searched using the same terms.
?The Author 2012.Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.All rights reserved.
Interactive CardioVascular and Thoracic Surgery 15(2012)498–504BEST EVIDENCE TOPIC -THORACIC
doi:10.1093/icvts/ivs175Advance Access publication 22May 2012
Table1:Relevant papers
Author,date and
country
Study type(level of
evidence)
Patient group Outcomes Key results Comments
Licker et al.(2003) Anesth Analg, Switzerland,USA[3] Prospective
case-control study (level III)n=879
Lung resections(all types)for
NSCLC
1991–2002
Fluid regimen:
1ml/kg/h in addition to
replacement of losses intra-
and postoperatively
PALI/ARDS:
37(4.2%)
(Using consensus criteria[4])
UVA:
Cumulated intra-and
postoperative crystalloid
fluid infusion ml/kg/h
(mean:95%CI):
PALI/ARDS group;
2.6ml/kg/h(2.3–2.9)
Non-PALI/ARDS group;
2.0ml/kg/h(1.7–2.3)
P=0.003
MVA:
Fluid infusion(cumulated
intra-and postoperative)
is associated with PALI/
ARDS by an OR of2.91
(95%CI:1.9–7.4)
P=0.001
Increasing fluid infusion is shown
to be associated with PALI/ARDS
by UVA and MVA
Factors included in the MVA:
Chronic alcohol excess
Pneumonectomy
Ventilatory hyperpressure
Fluid infused
Licker et al.(2009) Critical Care, Switzerland,USA[2] Retrospective
case-control study (level III)n=1091
Lung resection(all types)for
primary lung cancer
1997–2008
Fluid regimen:
Intraoperative crystalloid:
2–4ml/kg/h in addition to
replacement of losses
Protected lung ventilation
strategy group(2003–2008)
n=558
PALI/ARDS:
5(0.9%)
Standard ventilator strategy
group(1997–2003)
n=533
PALI/ARDS:
19(3.7%)
(Using consensus criteria[4])
Both cohorts had similar
baseline characteristics
UVA:
OR:1.33(95%CI:1.02–
5.08)per1ml/kg/h
increase in intra-and
postoperative fluid
administration
P=0.032
MVA:
OR:1.42(95%CI:1.09–
4.32)per1ml/kg/h
increase in intra-and
postoperative fluid
administration
P=0.011
Increasing fluid infusion is shown
to be associated with PALI/ARDS
by UVA and MVA
Factors included in the MVA:
Chronic alcohol excess
Chemoradiotherapy
Advanced TNM stage
Pneumonectomy
Fluid infused
Blank et al.(2011) Ann Thorac Surg, USA[6] Retrospective case-control study (level III)n=129
Pneumonectomy
1997–2008
Fluid regimen:
intraoperative fluid
management of1ml/kg/h
titrated to a mean arterial
pressure of75%of
preoperative average
All respiratory complications:
27(21%)
PALI/ARDS:
9(7%)
(Using consensus criteria[4])
UVA:
All respiratory
complications group:total
intraoperative fluid;
2.7l(95%CI:2.0–4.0)
No respiratory
complications group;
1.8l(1.5–
2.5)
P<0.001
MVA:
No significant association
Fluid is assessed against a
composite outcome of all
respiratory complications,not
individually against PALI/ARDS
Small cohort of PALI/ARDS cases
Factors included in MVA:
Blood product usage
Total fluids per litre
Surgical indication(benign vs
malignant)
Pneumonectomy type
Duration of anaesthesia
ASA status
Alam et al.(2007) Ann Thoracic Surg, USA[5] Retrospective case-control study (level III)n=152
Lung resection(all types)for
primary lung cancer
2001–2004
Fluid regimen:
Intraoperative fluid restriction
was used for all patients
Primary lung injury:
76(5.3%)
Primary lung injury=clinical
diagnosis of PALI/ARDS
without available arterial
blood-gas data
PALI/ARDS:
44(3.1%)
(Using consensus criteria[4])
UVA:
Primary lung injury group
(n=76):
Mean perioperative fluids
infused;
2.75l(95%CI:1.35–5)
Control group(n=76):
2.5l(1.4–4.5)
OR1.2(95%CI:1.0–1.4)
P=0.05
Evidence on MVA that increasing
perioperative fluid administration
is associated with‘primary lung
injury’
Absence of arterial blood gas data
on32patients means that the true
incidence of PALI/ARDS according
to[3]guidelines may be over-or
under-estimated.
Analysis of fluid volume against
confirmed cases of PALI/ARDS(44)
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Table1:(Continued)
Author,date and
country
Study type(level of
evidence)
Patient group Outcomes Key results Comments
MVA:
For every500ml increase in perioperative fluid administration:
OR1.2(95%CI:1–1.4)for postoperative primary lung injury
P=0.02was not performed Group matching: Smoking status Extended resection? Sex
pT,pN,pM status
Marret et al.(2010) Interact CardioVasc Thorac Surg,France [7] Retrospective case-control study (level III)n=129
Pneumonectomy
2000–2005
Fluid regimen:
Not defined
PALI/ARDS:
9(7%)
(Using consensus criteria[4])
UVA:
Total intra-and
postoperative fluid
infusion(l):
Patients with all major
complications(n=55);
3.8l±1.5(mean±SD)
Patients without major
complications(n=74);
2.5l±1.3(mean±SD)
OR:1.91(95%CI:1.47–
2.83)
P<0.0001
MVA:
OR1.96per litre increase
(95%CI:1.45–3.16)
P<0.0001
Total fluid infusion was assessed
against all major complications
rather than PALI/ARDS individually
on UVA and MVA
Small sample size(n=9)
Factors included in MVA:
ASA class
Age
Smoking history
COPD
Haemoglobin
Neutrophil count
Urea and creatinine
Total fluid infusion(l)
Peak pressure(cm water)
Tidal volume(ml/kg PBW)
Transfusion(%)
Operating time(min)
Fernandez-Perez et al.(2006) Anesthesiology, USA[8]
Retrospective case-control study (level III)n=170
Pneumonectomy
1999–2003
Fluid regimen:
Not defined
PALI/ARDS:
15(9%)
(Using consensus criteria[4])
Respiratory failure of other
aetiologies:
15(9%)
Total incidence of respiratory
failure:
30(18%)
UVA:
Respiratory failure of all
causes(30):
Median intraoperative
fluid volume infused:2.2l
(inter-quartile range:1.4–
3.7)
Patients without
respiratory failure(140):
Median intraoperative
fluid volume infused1.3l
(inter-quartile range:0.9–
2.7)
P<0.001
MVA:
Per litre of fluid infused
intraoperatively:
OR1.34(95%CI:0.83–
2.09)
P=0.201(not significant)
Fluid input was not directly
assessed against cases of PALI/
ARDS
No effect of increased fluid was
found on MVA
Factors included in MVA:
Intraoperative VT
Preoperative FVC
Fluid
Intraoperative VT x fluid
Parquin et al.(1996) Eur J Cardiothoracic Surg,France[11] Retrospective
case-control study (level III)n=146
Pneumonectomy
1992–1992
Fluid regimen:
Not defined
Pulmonary oedema within
first postoperative week:
22(15%)
Severe pulmonary oedema
within first postoperative
week:
5(3.4%)
Pulmonary oedema criteria:
Tachypnoea
UVA:
Total intraoperative fluid
load≥2l
Pulmonary oedema within
first postoperative week
(n=22):10(45%)
Control group(n=124):
25(20%).
P<0.01
No arterial blood gas data
Consensus criteria[4]are not used
Data confounded by mild
pulmonary oedema
Impossible to directly compare
this study to others
Factors included in MVA: R.G.Evans and B.Naidu/Interactive CardioVascular and Thoracic Surgery
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Table1:(Continued)
Author,date and
country
Study type(level of
evidence)
Patient group Outcomes Key results Comments
Crackles
Edematous Sputum Diffuse infiltrates on chest radiographs MVA:
Total intraoperative fluid
load≥2l is associated with
pulmonary oedema of all
severities(P=0.02)
Prior radiotherapy
Total fluid load≥2l
Remaining lung perfusion≤55%
Moller et al.(2002) Eur Resp J, Denmark[9] Retrospective case-control study (level III)n=107
Pneumonectomy
4-year period
Fluid regimen:
Normal saline0.9%was
administered at5ml/kg/h
intraoperatively
Pulmonary complications
(all):
19(7.8%)
No measurement of
incidence of PALI/ARDS
UVA:
>4l during anaesthesia(n
=13)
38.5%developed
pulmonary complications
<4l during anaesthesia(n
=92)
15.2%developed
pulmonary complications
P<0.05
>4l fluid balance group
associated with higher
mortality(30.8vs7.6%,
P<0.05)
MVA:
Intraoperative fluid
balance>4l
OR4.48(95%CI:1.05–
19.02)
P=0.042
No analysis of mortality
on MVA
Consensus criteria[4]are not used
Fluid balance/excess is not
specifically analysed against PALI/
ARDS
Rationale for large volumes of
intraoperative fluid administration
not given
Possibility data is confounded by
blood loss
Factors included in the MVA:
Age>70
Pre-op heart disease
BMI<17or>25
Pneumonectomy(right)
Anaesthesia>360min
Fluid excess>+4l
Bernard et al.(2001) J Thorac Cardiovasc Surg,USA[10] Retrospective cohort study
(level III)n=639
Pneumonectomy
1985–1998
Fluid regimen:
Not defined
Post-pneumonectomy
pulmonary oedema(PPPE):
7(1.1%)
UVA:
IV fluid variables
associated with
cardiopulmonary
complications(all causes):
IV crystalloid first24h
(including intraoperative
fluids)
(P=0.01)
IV crystalloid first12h
(including intraoperative
fluids)
(P=0.01)
IV fluid variables
associated with mortality:
IV crystalloid first12h
(P=0.01)
MVA:
No significant associations
with IV crystalloid
PPPE is not defined
Consensus criteria[4]are not used
Primary data relating to fluid
administration are unpublished
Study is not controlled
Fluids are not directly assessed
against PALI/ARDS
Factors included in MVA:
Increased age
Cardiovascular disease
Muscle reinforcement of bronchial
stump
Ruffini et al.(2001) Eur J Cardiothoracic Surg,Italy[15] Retrospective
case-control study (level III)n=1221
Lung resection(all types)for
lung cancer
1993–1999
PALI/ARDS:
27(2.2%)
(Using consensus criteria[4])
No evidence of an
association between fluid
intake and PALI/ARDS
Primary data relating to fluid
administration is unpublished
Intraoperative fluid restriction of
<1500ml may account for the low
incidence(2.2%)of PALI/ARDS
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Table 1:(Continued )
Author,date and country
Study type (level of evidence)
Patient group
Outcomes
Key results
Comments
Crystalloid
Intraoperative fluid restriction of <1.5l
1.5l of crystalloid over 48h postoperatively
Kutlu et al.(2000).Ann Thorac Surg,UK [14]
Retrospective
case-control study (level III)
n =1139
Lung resections (all types)1991–1997Fluid regimen:Not defined PALI/ARDS:45(3.9%)
(Using consensus criteria [4])
No evidence of fluids as a risk factor
Primary data relating to fluid administration is unpublished
Van der Werff et al.(1997)Chest,Netherlands [12]Retrospective
case-control study (level III)
n =197
Pneumonectomy 1989–1995Fluid regimen:Not defined Postoperative pulmonary oedema (PPE):29(14.7%)
No evidence of fluids as a risk factor for PPE
Primary data relating to fluid administration is unpublished Consensus criteria [4]are not used therefore incidence of PALI/ARDS may be over-/under-estimated
Hayes et al.(1995)Thorax,UK [13]Retrospective
case-control study (level III)
n =469
Lung resections (all types)1991–1994Fluid regimen:Not defined
PALI/ARDS:22(5.1%)
(Using consensus criteria [4])
No evidence of fluids as a risk factor
Primary data relating to fluid administration is unpublished
Zeldin et al.(1984)J Thorac Cardiovasc Surg,USA [17]Retrospective unmatched
case-control study of selected patients (level IV)
n =25
Pneumonectomy
Pulmonary oedema:10Uncomplicated
pneumonectomy:15
Fluid intake (pulmonary oedema group):4913±1169ml (mean ±SD)
Fluid intake (uncomplicated
pneumonectomy group):3483±984ml
Consensus criteria [4]post-date the study
Severity of pulmonary oedema is not described
Cases and controls are not matched
Zeldin et al.(1984)J Thorac Cardiovasc Surg,USA [18]Experimental canine animal study
n =13
A (n =8):100ml/kg crystalloid immediately prior to right pneumonectomy followed by >100ml/kg postoperative fluid balance
B (n =5):50ml/kg
immediately prior to right pneumonectomy followed by 50ml/kg intraoperatively followed by <100ml/kg postoperative fluid balance C (n =4):100ml/kg
immediately prior to sham thoracotomy followed by >100ml/kg postoperative fluid balance
Pulmonary oedema:62dogs in group A died prematurely
(Left lung weight/right lung weight ratio >1)
(Left lung/body weight ratio >0.68)
All dogs received 4ml of fluid for every millilitre of intraoperative blood loss
Group A:all surviving dogs developed pulmonary oedema
Group B:no dogs developed pulmonary oedema
Group C:no dogs developed pulmonary oedema
Fluid regimens described are not directly comparable to medical practice
Severity of pulmonary oedema is not described in
clinically-translatable terms Powerful demonstration of the pathophysiology of
pneumonectomy exposing the remaining lung to a risk of pulmonary oedema
Evidence of a link between
post-pneumonectomy pulmonary oedema and large fluid load in mammals
UVA:univariate analysis;MVA:multivariate analysis;PALI:postoperative acute lung injury;ARDS:acute respiratory distress syndrome;NSCLC:non-small cell lung cancer.
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SEARCH OUTCOME
Sixty-seven papers were found using the reported search. Fourteen papers were selected as giving the best evidence (Table1).
RESULTS
The best evidence available to answer this question are the studies by Licker et al.[2,3].Both used consensus guideline criteria[4]for the diagnosis of PALI/ARDS and demonstrated an association between increasing the volume of?uid admin-istration in the intraoperative and postoperative periods and the incidence of PALI/ARDS on multivariate analysis(MV A) with odds ratios(ORs)of1.42(95%CI1.09–4.32,P=0.011)[2] and2.91(1.9–7.4,P=0.001)[3].In non-PALI/ARDS cases,the mean intraoperative?uid infusion volume was signi?cantly less (1.22l(1.17–1.26)vs1.68l(1.46–1.9)P=0.005),?uid balance over the?rst24postoperative hours was signi?cantly less (1.52l positive(1.44–1.60)vs2.0l positive(1.6–2.4)P=0.026) and cumulated intra-and postoperative?uid infusion was also signi?cantly less(2.0ml/kg/h(1.7–2.3)vs 2.6ml/kg/h (2.3–2.9)P=0.003)[3].Total?uid infusion in the?rst24h postoperatively was not signi?cantly different(PALI/ARDS group 2.1l(1.85–2.33),non-PALI/ARDS group 1.85l(1.79–1.91)P=0.075)[3].This data set provides evidence that the difference between?uid therapy associated with an increased incidence of PALI/ARDS(i.e.‘liberal’)and?uid therapy asso-ciated with no increased incidence(i.e.‘conservative’)is narrow,although it is not possible to provide an exact de?n-ition of liberal?uid therapy from these data.Alam et al.[5] also demonstrated a signi?cant association on MV A between increasing?uid administration and the outcome‘primary lung injury’(OR1.2(1–1.4),P=0.02)for every500ml increase in perioperative?uid administration;however,this study was limited by the use of non-standardized diagnostic criteria for PALI/ARDS,raising the potential for an over-or under-diagnosis of the condition.
Several of the other studies analysed were limited in that ?uids were not directly assessed against PALI/ARDS;composite outcome measures such as‘all respiratory’or’all major’compli-cations were used[6–10].Others were limited for the purposes of comparison by using non-standardized outcomes related to PALI/ARDS,e.g.‘primary lung injury’and‘postoperative pulmon-ary oedema’[5,9–12]rather than consensus criteria[4].Where no association is reported,several papers have not published the amount of?uid administered[10,12–15].Blank et al.[6]may have shown an association between?uid intake and the outcome‘all respiratory complications’were the cohort of PALI/ ARDS cases larger(n=9)[16].
The published data show that liberal?uid therapy is asso-ciated with a higher incidence of PALI/ARDS;however,a causal relationship cannot be inferred;PALI/ARDS is clearly a multifactorial disease process with liberal?uid therapy being one of several associated risk factors(e.g.blood transfusion, hypotensive haemorrhage,prolonged duration of one-lung ventilation and ventilator-induced lung injury).It is thought that the development of PALI/ARDS may require two or more of these‘hits’[17].The evidence presented here follows on from the1984unmatched case–control study[18]of25patients which suggested that a liberal vs judicious periopera-
tive?uid load is associated with pulmonary oedema following pneumonectomy(4913±1169ml(n=10pulmonary oedema cases)vs3483±984ml(n=15controls)(mean±SD)).This study also described a canine experimental model of right pneumonectomy with a48h period of postoperative moni-toring that assessed a liberal crystalloid perioperative?uid load (100ml/kg rapidly infused immediately preoperatively followed
by a>100ml/kg postoperative?uid balance(n=8))vs a judi-cious perioperative?uid load(50ml/kg rapidly infused imme-diately preoperatively followed by50ml/kg rapidly infused intraoperatively followed by a<100ml/kg postoperative?uid balance[n=5])vs a control group with a100ml/kg preopera-
tive rapid?uid load followed by sham thoracotomy and>100
ml/kg postoperative?uid balance.All dogs in the liberal?uid
load group developed pulmonary oedema,whereas no dogs in
the judicious?uid load or control group developed the condition.
The control group data powerfully demonstrate that the peri-operative pathophysiology of pneumonectomy exposes the remaining lung to a risk of pulmonary oedema in mammals. CLINICAL BOTTOM LINE
PALI/ARDS has a mortality of>50%[19];therefore,strategies to reduce its incidence are of great interest.On this best evidence presented,we recommend a conservative strategy of administra-
tion of maintenance?uids at1–2ml/kg/h in the intra-and post-operative periods and that a positive?uid balance of1.5l should
not be exceeded,to mitigate the risk of multifactorial PALI/ ARDS.Caution should be exercised with regard to silent hypo-volaemia,impaired oxygen delivery and acute kidney injury[20].
If the?uid balance exceeds this threshold,a high index of suspi-
cion for PALI/ARDS should be adopted and an escalation of the level of care should be considered.If a patient develops signs of hypoperfusion after these thresholds are exceeded,inotropic/ vasopressor support should be considered.
Con?ict of interest:none declared.
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