Assessing Fluid Responsiveness in Critically Ill Patients Justin Hourmozdi MD Henry Ford Hospital, Department of Emergency Medicine, EM 2.5 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 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 and is becoming hypotensive requiring escalating doses of Levophed over the next 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 hes 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 ). 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 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 = 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. 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 mmHg 20 mmHg Normal LV with high EDVPoor LV with reduced compliance and lower EDV 20 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 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 13 where a correlation could exist. Re-evaluated CVP for FR looking at a larger sample subgrouped by CVP studies included, raw data sets were obtained from PIs from each study, of which the majority had mean CVP values in the 8-12 range. 1,148 patients allowed subgroup analysis of CVP 12 groups in which the lower 95% CI crossed 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 (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 studies included, raw data sets were obtained from PIs 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 12 groups in which the lower 95% CI crossed 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 (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 studies included, raw data sets were obtained from PIs 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 12 groups in which the lower 95% CI crossed 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 (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 =15% predicted fluid responsiveness in 2 small studies. Theses patients were mechanically ventilated with TV 8-10 ml/kg, PEEP 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 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 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 +/ Excluded patients on hemodialysis, ascites, afib, and HR >120. Results/Conclusion: dIVC correlated well with ROC curve of 0.81; while SVV was 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.