Download Routine chest radiography is not necessary after

Assessing Fluid Responsiveness in
Critically Ill Patients
Justin Hourmozdi MD
Henry Ford Hospital, Department of Emergency
Medicine, EM 2.5
S
Objectives
• Review the clinical significance and literature on
the topic
• Specifically review the literature regarding
common modalities used in the ED and ICU to
assess fluid responsiveness including: physical
exam, CVP, IVC ultrasound, and pulse contour
analysis (SVV/PPV), EDM
Definitions
Fluid Responsiveness refers to the ability of the
heart to accept a fluid challenge and increase cardiac
output, generally defined as a rise of 10-15%, using
most PAC, thermodilution techniques or TEE.
Is my patient fluid responsive?
79 year old male who presents to the ED in septic
shock with pneumonia. You have intubated the
patient, placed a CVL and a-line, given 4L of IVF to
achieve a CVP of 10-12, and started Levophed to
maintain MAP. SvO2 is 68%. There are no MICU
beds, and you are now caring for the patient for 8-9
hours and have to sign out to the oncoming team.
Throughout your shift, the patient is having
escalating Levophed requirements, O2/PEEP
requirements and plateau pressures. The patient is
in oliguric renal failure. Should you give more
volume, keep increasing the Levophed?
Is my patient fluid responsive?
54 year old female admitted directly to GPU from clinic with
“sepsis” of unknown origin. The patient is spiking low-grade
fevers and tachycardic with low UOP and rising Cr. The GPU
team gives several liters of IVFs over the next 24-36 hours
empirically. The patient has increased oxygen requirements
and goes into hypertensive emergency and respiratory distress
and gets intubated in the MICU. You line the patient up and
she has a CVP of 12-14 and is becoming hypotensive
requiring escalating doses of Levophed over the next 12-24
hrs. She is in oliguric renal failure and your urine lytes
indicate she is pre-renal. Her vent requirements are increasing
to PEEP of 18, CXR is “fluffy”. Volume challenge? Increase
pressors? Dialysis?
Is my patient fluid responsive?
48 year old male with a history of uncontrolled hypertension
comes to the ED with a 2 day history of N/V and unable to
take his meds. He is severely hypertensive. You give him all his
home meds and several doses of IV antihypertensives and get
an ICU bed quickly. The patient is still hypertensive and a
Nicardipine drip is started and maxed out, probably when his
oral meds start to have peak effect. The patient goes into shock,
gets intubated, and is in anuric renal failure. His CVP is 14-16,
CXR showed mild pulmonary edema, his lower extremities
have 1+ pitting edema, and he’s on high doses of Levophed
with a lactate of 16. You receive the patient with instructions to
call Nephrology to remove volume. His Vigeleo shows a CI of
1.6 and SVV of 18.
Conclusions up front
• Over-resuscitation with fluids leads to increased morbidity and mortality in
critically ill patients.
• CVP is a practical and valid tool during the initial phase of resuscitation (6-12
hours) to assess volume tolerance and to “fill the tank” before starting
vasopressors. SSG state best evidence is to achieve filling CVP of 8-12 within
first 6 hours, however there is no clear evidence on when to discontinue or
reduce fluid resuscitation after that point.
• After this initial phase of resuscitation, ideally additional modalities should be
used in conjunction with CVP to assess whether further fluid resuscitation is
needed. IVC ultrasound and SVV/PPV are two of the more validated and
practical modalities, however each have their limitations. Patients must be
mechanically ventilated with TV in 8-10 ml/kg range. Additionally for
SSV/PPV analysis, patients must be in NSR, no significant cardiac disease,
and sedated and synchronous with the ventilator.
Fluid balance and Prognosis
Unguided large-volume resuscitation has been shown to increase
extravascular lung water and resultant increased time on MV, increased ICU
LOS and mortality. Also there is some evidence suggesting an increase in
AFF and RRT.
Survey of critically ill patients with sepsis, positive fluid balance was associated with increased mortality. Vincent JL, Sakr Y,
Sprung CL, et al: Sepsis in European intensive care units: Results of the SOAP study. Crit Care Med 2006
Positive fluid balance increased time on ventilator and trend towards increased mortality in critically ill patients with ALI.
Wiedemann HP, Wheeler AP, Bernard GR, et al: Comparison of two fluid management strategies in acute lung injury. N Engl J Med 2006
Systematic review of all RCT of goal-directed fluid resuscitation reporting renal outcomes during perioperative care. In 24
perioperative studies, GD-FR was associated with decreased risk of postoperative AKI (OR 0.59, 95% CI 0.39-0.89).
Prowle JR, Chua HR, Bagshaw SM, et al: Clinical review: Volume of fluid resuscitation and the incidence of acute kidney injury – a systematic
review. Crit Care 2012
Examining the PROCCES data, protocol-based standard-therapy group received on average more IVFs and had higher incidence of ARF
needing RRT than in the EGDT and usual care groups (6% vs 3%).
Objective: To determine whether CVP and net fluid balance after resuscitation for septic
shock are associated with mortality.
Methods: 778 patients from multiple centers, retrospective review of the use of IVFs after the
first 12 hours and up to 4 days.
Results/Conclusion: A more positive fluid balance at both 12 hours and day 4 correlated
significantly with increased morality. Highest survival was seen with a fluid balance of +3L at
12 hours. CVP correlated modestly with fluid balance at 12 hours (R correlation 0.2 and
p<0.001), whereas on days 1-4 there was no significant correlation. At 12 hours, patients with
CVP <8 had the lowest morality rate, followed by 8-12, and the highest mortality was seen in
those with CVP >12. A more positive fluid balance both early in resuscitation and over 4
days is associated with increased mortality. CVP may be used to gauge fluid balance <12
hours into resuscitation.
Objective: To determine whether CVP and net fluid balance after resuscitation for septic
shock are associated with mortality.
Methods: 778 patients from multiple centers, retrospective review of the use of IVFs after the
first 12 hours and up to 4 days.
Results/Conclusion: Average fluid balance at 12 hours was +4.2L with average of 6.3L
given. A more positive fluid balance at both 12 hours and day 4 correlated significantly with
increased morality. Highest survival was seen with a fluid balance of +3L at 12 hours. CVP
correlated modestly with fluid balance at 12 hours (R correlation 0.2 and p<0.001), whereas
on days 1-4 there was no significant correlation. At 12 hours, patients with CVP <8 had the
lowest morality rate, followed by 8-12, and the highest mortality was seen in those with CVP
>12. A more positive fluid balance both early in resuscitation and over 4 days is associated
with increased mortality. CVP may be used to gauge fluid balance <12 hours into
resuscitation.
• Was mortality higher in the higher fluid balance and CVP group because this was a sicker subset
of patients?
• “CVP <8 at 12 hours was associated with improved survival compared with 8-12 and >12
groups.” Why is this? This study did not look at CVP at time 0, 3, 6 hours. At 12-36 hours, if the
patient is improving, their hemodynamic state improves, CO and UOP improves, CVP drops,
and they do better. This does not mean the patient is becoming dehydrated as they are improving.
This does not mean to aim for CVP <8 at 12 hours either.
• CVP doesn’t correlate well with fluid balance later on likely because of third spacing occurring
after initial hours of fluid resuscitation, CVP is a measure of intravascular pressure behind the
right heart, not total body volume.
• The patients in the driest quartile received the least average IVFs (2900) and had the most UOP
(2200), whereas the wettest group received the most IVFs (10,100) despite having the lowest
UOP (1260). Where these trends due to the clinician using UOP as a guide for fluid prescription?
Why might have the majority of clinicians continued to give IVFs despite achieving a CVP of 812?
• Was mortality higher in the higher fluid balance and CVP group because this was a sicker subset
of patients?
• CVP <8 at 12 hours was associated with improved survival compared with 8-12 and >12 group.
Why is this? This study did not look at CVP at time 0, 3, 6 hours. At 12-36 hours, if the patient is
improving, their hemodynamic state improves, cardiac output improves, UOP improves, CVP
drops, and they do better. This does not mean the patient is becoming dehydrated as they are
improving. This does not mean to aim for CVP <8 at 12 hours either. CVP <8 had only a slight
mortality advantage compared with 8-12, and both were significantly better off than >12.
• CVP doesn’t correlate well with fluid balance later on likely because of third spacing occurring
after initial hours of fluid resuscitation, CVP is a measure of intravascular pressure behind the
right heart, not total body volume.
• The patients in the driest quartiles received the least average IVFs (2900) and had the most UOP
(2200), whereas the wettest group received the most IVFs (10,100) despite having the lowest
UOP (1260). Where these trends due to the clinician using UOP as a guide for fluid prescription?
Why might have the majority of clinicians continued to give IVFs despite achieving a CVP of 812?
Objective: Hypothesized that there is an association between quicker, adequate fluid
resuscitation and patient outcome from sepsis onset time.
Methods: 594 patients, retrospective review. Adjusted for total fluid administration within
the first 6 hours of sepsis onset, additionally adjusted for age and severity scores. Outcome
was in-hospital mortality.
Results: Median amount of fluid within first 3 hours for survivors was 2,085 mL (9404,080) vs non-survivors 1,600 mL (600-3,010) [p=0.007]. In comparison, during the 3-6
hours, 660 mL vs 800 mL (p=0.09). The higher proportion of total fluid received within
the first 3 hours was associated with decreased hospital mortality (OR 0.34, 95% CI 0.150.75, p=0.008).
Objective: To determine the role of fluid resuscitation in the treatment of children
with septic shock and life-threatening infections. Most children in hospitals in subSaharan Africa receive no specific fluid management apart from blood transfusion for
severe anemia or MIVFs. They wanted to compare international standard of practice
(bolus-fluid resuscitation) to local standard of care (no bolus-fluid resuscitation).
Methods: MC-RCT of 3,141 children in Africa. 3 groups: 5% Albumin bolus, NS
bolus, no bolus for children with severe febrile illness and impaired perfusion (AMS,
resp distress, cap refill >3s, cool exts, weak pulse, severe tachycardia, 39% lactate >5).
Children with severe hypotension were randomly assigned to bolus groups only.
Primary end-point was 48-hr mortality, secondary included 28-day mortality.
Results: 48-hr mortality was 10.6%, 10.5%, and 7.3%, 28-day mortality was 12.2%,
12%, 8.7% (p=0.004 for any bolus vs control).
Physical Exam
•
Systematic review of 10 studies investigating postural vital signs or cap refill of
healthy volunteers who underwent phlebotomy. Most helpful physical findings are
severe postural dizziness, postural pulse increase of >= 30 (measured 1 minute after
standing). Presence of either finding has a sensitivity of only 22% for moderate
blood loss (~500mL), but much greater sensitivity for large (~1L) blood loss (97%)
and specificity (98%).
•
Postural hypotension (drop in SBP >20) was not sensitive nor specific, and occurs in
up to 10% or normovolemic adults <65 and 11-30% >65. A study of 911 elderly
NH patients in this review found that about 50% were orthostatic.
•
Four studies of patients presenting to the ED with suspected hypovolemia due to
N/V/D. The presence of a dry axilla supports hypovolemia (LR+2.8) and moist
MMs and a tongue without furrows argue against it (LR-0.3). In adults, cap refill
and skin turgor have no proven diagnostic value.
One of the more recent of a number of trials showing that estimation of volume status
in critically ill patients based on physical exam showed poor correlation with volume
status and poor interobserver agreement.
•
Physical exam is unreliable in assessing volume status, especially in critically ill
patients. Vital signs can be non-specific, UOP can be misleading if in ATN,
peripheral edema does not always correlate with intravascular volume status, skin
and mucus membrane changes are subject to interobserver variability,
environmental conditions, medications (anticholinergic effects of many
medications).
•
Just give a bolus and reassess physical exam: check RR, pulse ox and listen for
crackles, but should pulmonary edema really be an end point of fluid resuscitation?
Central Venous Pressure
CVP is a good approximation of RAP, which is a major determinant of RV
filling. Assuming that CVP is a good indicator of RV preload and because
RV SV determines LV preload, then CVP is assumed to be an indirect
measure of LV preload. CVP is influenced by the patients’ vascular tone
and hemodynamic status, RV and LV compliance, lung compliance,
presence of tricuspid valve abnormalities, pulmonary hypertension, and
intraabdominal pressure. Therefore, CVP is best interpreted in the clinical
context of the patient, using other hemodynamic and metabolic end-points.
Pressure or Volume?
20
Normal LV with high EDV
Poor LV with reduced
compliance and lower EDV
•
Systematic review and meta-analysis was performed to determine relationship
between CVP and blood volume and fluid responsiveness.
•
24 studies included, with a total of 830 patients. 5 studies compared CVP with
measured circulating blood volume. 19 studies determined the relationship
between CVP/dCVP and fluid responsiveness. Overall, about half of patients
were fluid responsive. Pooled correlation coefficient between CVP and blood
volume was 0.16. The pooled correlation coefficient between CVP/dCVP and
fluid responsiveness was 0.18 and 0.11, respectively. The pooled area under the
ROC curve was 0.56 with CIs crossing 0.50, meaning that at any CVP the
likelihood that CVP accurately predicts fluid responsiveness is “similar to flipping
a coin”.
•
Baseline CVP was 8.7+/-2.3 in responders compared to 9.7+/-2.2 in
nonresponders (non-significant difference). Is this a collection of mostly volume
replete ICU patients, most of whom are several days into their hospital course?
•
True, small differences in target-range CVPs may not predict volume
responsiveness, but patients who are very dry often have CVP values of <5 that
will significantly increase after volume expansion. I believe there is insufficient
evidence from this review to show lack of relationship for CVP during the initial
phase of resuscitation, and possibly at more extreme values, such as <5 or >13
where a correlation could exist.
• Re-evaluated CVP for FR looking at a larger sample subgrouped by CVP <8, 812, >12. 51 studies included, raw data sets were obtained from PI’s from each
study, of which the majority had mean CVP values in the 8-12 range.
• 1,148 patients allowed subgroup analysis of CVP <8, which showed area under
ROC curve of 0.57 (95% CI 0.52-0.62), in contrast to the CVP 8-12 and >12
groups in which the lower 95% CI crossed 0.50.
• Identified some modest PPV/NPV for low/high CVP values. The highest PPV
was at CVP cut-off of 2-4 (65%) and NPV at CVP cut-off of 14-16 (66%).
About 2/3 were MV with TVs ranging from 5-12 ml/kg.
• Re-evaluated CVP for FR looking at a larger sample subgrouped by CVP <8, 812, >12. 51 studies included, raw data sets were obtained from PI’s from each
study, of which the majority had mean CVP values in the 8-12 range.
• Analysis of 1,148 patients from 22 studies allowed subgroup analysis of CVP
<8, which showed area under ROC curve above 0.50 (0.57, 95% CI 0.52-0.62),
in contrast to the CVP 8-12 and >12 groups in which the lower 95% CI crossed
0.50. Identified some modest PPV/NPV for low/high CVP values. The highest
PPV was at CVP cut-off of 2-4 (65%) and NPV at CVP cut-off of 14-16 (66%).
About 2/3 were MV with TVs ranging from 5-12 ml/kg.
• Re-evaluated CVP for FR looking at a larger sample subgrouped by CVP <8, 812, >12. 51 studies included, raw data sets were obtained from PI’s from each
study, of which the majority had mean CVP values in the 8-12 range.
• Analysis of 1,148 patients from 22 studies allowed subgroup analysis of CVP
<8, which showed area under ROC curve above 0.50 (0.57, 95% CI 0.52-0.62),
in contrast to the CVP 8-12 and >12 groups in which the lower 95% CI crossed
0.50. Identified some modest PPV/NPV for low/high CVP values. The highest
PPV was at CVP cut-off of 2-4 (65%) and NPV at CVP cut-off of 14-16 (66%).
About 2/3 were MV with TVs ranging from 5-12 ml/kg.
IVC Ultrasound
Distendibility index of IVC of >=15% predicted fluid
responsiveness in 2 small studies. Theses patients were
mechanically ventilated with TV 8-10 ml/kg, PEEP <10.
dIVC = Dmax-Dmin/Dmin x100
IVC Ultrasound
Distendibility index of IVC of >=15% predicted fluid
responsiveness in 2 small studies. Theses patients were
mechanically ventilated with TV 8-10 ml/kg, PEEP <10.
dIVC = Dmax-Dmin/Dmin x100
Methods: 23 patients with septic shock and mechanically ventilated. CI was
determined by ECHO doppler of the PA trunk. CI measured before and after a
7ml/kg bolus.
Results: Using a threshold of dIVC of 18%, responders and non-responders were
discriminated with a 90% sensitive and specificity. Of note, MV parameters were
TV 8.5+/-1.5 ml/kg, PEEP <10, Plat Pressure <30.
Methods: 39 patients with septic shock and MV. Patients were again ventilated
with TV of 8-10ml/kg. CO was assessed by ECHO (measuring the diameter of
the aortic orifice and the velocity time integral of aortic blood flow during endexp before and after fluid bolus).
Results: Very close relationship was observed with pre-infusion dIVC (r=0.82,
p<0.001), and 12% dIVC cut-off value allowed identification of responders with
PPV 93% and NPV 92%.
Objective: Determine if dIVC is an accurate measurement of FR in non-MV ED
patients.
Methods: 26 non-MV patients. FR asssessed by impedance cardiography following
passive leg raise.
Results: dIVC did not predict FR (receiver operating curve=0.46, P=0.63).
Objective: Compare the effect of ECHO-guided therapy to standard management
(EGDT) following “early resuscitation for shock”, which means they were enrolled
after the treating team had achieved SSG targets of CVP 8-12 and were then
requiring pressors to maintain MAP>65.
Methods: 220 septic and cardiogenic shock patients, 110 studied prospectively in
ECHO group over 1 year, and 110 studied retrospectively in the year prior. All
patients were MV. ECHO was performed within 24 hrs of admission. dIVC >15%
were considered volume responsive.
Results: Prior to enrollment, patients had received about 65 ml/kg, achieved a
CVP of >8, on Levo at ~10mcg on average, and had cleared their lactate
elevations. ECHO group during first 24 hrs had significantly lower fluid
prescription (49 vs 66 ml/kg, p=0.01), reduced stage 3 AKI (20% vs 39%), more
days alive and free of RRT (28 vs 25 days), and improved 28-day survival (66% vs
56% p=0.04).
• This study is again looking at the sub-acute phase of shock after
the initial resuscitation using end-points like CVP and MAP, and
provides some evidence that this method of limiting fluids after the
initial phase of resuscitation may improve outcomes.
• Obvious weakness is the methodology and non-randomized nature
of the study.
Pulse Contour Analysis (SVV/PPV)
To use pulse contour analysis patient must have an arterial line, mechanical
ventilation with TV 8-10 ml/kg, NSR, no valvular heart disease, deeply sedated and
synchronous with ventilator. In general, SVV >12% is considered to be FR.
Positive pressure ventilation induces cyclic changes in the loading
conditions of the LV and RV, which are exacerbated during times of low
preload, or on the steep portion of the Frank-Starling curve.
• 568 critically ill patients from 23 studies.
• SVV was correlated to FR with a pooled correlation coefficient of 0.72,
pooled AUC of 0.84 and a sensitivity and specificity of about 80% for
predicting FR, improved to about 85% in the ICU vs OR subgroup.
• Most patients were MV with TV >8ml/kg, although 5 studies used slightly
lower TVs. A number of studies excluded patients with low EF (usually
<30%) and high BMI (>40).
• Looked at association between SVV and PPV and FR. 685 patients from
29 studies (258 patients from 12 studies looking specifically at SVV).
• The correlation between SVV and change in CI was very similar (r=0.72,
AUC=0.84, sensitivity 82% and specificity 86%). The correlation with
PPV was even better (r=0.78, AUC=0.94, sensitivity 89% and specificity
88%).
• 2/12 studies assessed SVV in cardiac surgery patients with reduced EF vs
normal EF and both studies demonstrated that the performance of SVV
was similar in both subgroups.
IVC variation compared to pulse contour analysis as predictors of fluid
responsiveness: a prospective cohort study. 2011. J of Int Care Med. (abstract
only)
Objective: To simultaneously assess ability to predict FR using SVV obtained with
Vigileo and dIVC in critically ill patients on MV.
Methods: 25 MICU patients (12 ARDS, 10 sepsis, 3 cardiac arrest) undergoing
MV that required vasopressors, had worsening organ function and were well
adapted to the ventilator. TV was 8.6 ml/kg +/- 1.7. Excluded patients on
hemodialysis, ascites, afib, and HR >120.
Results/Conclusion: dIVC correlated well with ROC curve of 0.81; while SVV
was 0.57. dIVC is superior to SVV obtained with Vigileo (possibly due to lack of
calibration, unlike PiCCO).
Esophageal Doppler Monitor
Conclusion
• Despite what the nay-sayers claim, CVP is still a practical and valid tool
during the initial phase of resuscitation.
• Be mindful when using CVP during that initial phase, and more
importantly afterwards. After initial goals are met, ideally additional
modalities should be used to guide fluid prescription, and this phase is also
critical in the morbidity and mortality of your patients. However, these
modalities are not without their own specific practical limitations.