Central venous access has long been considered to be an essential tool for the management of critically ill patients in the emergency department and the intensive care unit. Not only does it provide a mean for invasive monitoring (central venous pressure, CVP) and measurement of physiologic parameters (central venous oxygenation, ScvO2), but it also allows for the safe infusion of vasopressors and inotropes. Nevertheless, critically ill patients can sometimes be managed without central venous access, at least temporarily. In this post we will present possible alternatives to CVP and ScvO2, as well as provide vasopressor dilutions that can be used via peripheral venous access.
Alternatives to CVP:
Central venous pressure is heavily engrained as an important determinant of volume status and fluid responsiveness. It is also considered to be an essential step of early goal directed therapy (EGDT) for sepsis, as outlined by the landmark paper by Rivers et al. Many fail to realize however that fluid resuscitation to achieve a CVP of 8-12 mmHg was performed in both the control and the intervention groups in this study. Therefore, it’s usefulness was not established in this trial. A number of studies performed in intensive care settings have failed to show CVP as a reliable indicator of fluid responsiveness, and a systematic review by Marik et al. published in 2008 also came to the same conclusion. The physiologic limitations of CVP, such as its inability to differentiate between changes in volume (preload) and changes in cardiac function (contractility and cardiac output), are nicely explained in an article by Drs. Bigatello and George.
1) Physical Examination:
While clinical signs of dehydration can be reliably assessed in children (prolonged capillary refill, poor skin turgor, dry mucous membranes), it is not clear if physical examination alone can be used to determine fluid status in critically ill adult patients. A paper published in JAMA in 1999 as part of the “Rational Clinical Examination” series attempted to answer this question by systematically reviewing the literature pertaining to the physical diagnosis of hypovolemia in adults. We summarized the results below, focusing on hypovolemia from causes other than acute blood loss. It is important to realize that the studies used in this review were done on patients with vomiting, diarrhea, or decreased oral intake, as opposed to distributive shock. Additionally, patients in critical condition were excluded from some of these studies.
In patients with volume depletion (not from blood loss), the presence of a dry axilla supported the diagnosis of hypovolemia (+LR, 2.8), while moist mucous membranes, a tongue without furrows (-LR, 0.3 for both findings), and the absence of sunken eyes (-LR, 0.5) argued against it. The capillary refill time and poor skin turgor had no proven diagnostic value.
Despite these findings, it is unlikely that physical examination alone will be sufficient to determine fluid status, and more importantly fluid responsiveness in a population of critically ill patients. Other ways of accomplishing this however are presented below.
2) Sonographic Assessment of Inferior Vena Cava Collapse (∆IVC):
How to do it: Measurement of IVC collapse is increasingly used as a non invasive variant of CVP to determine fluid status in critically ill patients. This technique consists of obtaining a longitudinal ultrasonographic view of the IVC as in enters the right atria. To perform this, the low frequency ultrasound probe is placed in the subxyphoid area and angulated towards the patient's head (see picture). An image similar to that of Figure 1 should be obtained. Once the IVC is visualized, its maximum and minimum diameters are observed and recorded over one respiratory cycle. Alternatively, the variation of the IVC diameter can be observed in M-mode to facilitate measurements (see Figure 4). The percentage variation (or collapse) can then be calculated using the following formula:
ΔIVC = (IVCMAX - IVCMIN) / [(IVCMAX + IVCMIN) / 2] x 100%
IVCMAX = maximum IVC diameter, IVCMIN = minimum IVC diameter (see Figure 4).
A detailed description of how to perform the IVC ultrasound can be found here.
While the IVC will collapse with inspiration in a spontaneously breathing patient, the reverse will be true in a patient that is mechanically ventilated.
How to interpret the numbers: An IVC collapse of 50% or more would correspond to a CVP of less than 8 mmHg, indicating the patient should receive more fluids.
Caveat: Given that IVC variation follows the same physiologic principle as CVP, it is associated with the same limitations as the latter (see introduction).
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| Placement of probe for longitudinal IVC view |
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| Figure 1 in Nagdev et al., 2009: Ultrasonographic determination of inspiratory inferior vena cava (IVCi) and expiratory inferior vena cava (IVCe). |
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| Figure 4 in Goldflam et al., 2011: Inferior Vena Cava Ultrasound |
While the study by Nagdev et al looked at the correlation between an IVC collapse of 50% or more and a CVP of less than 8 mmHg, it is important to keep in mind that an increase in cardiac output (CO) remains the gold standard for determination of fluid responsiveness (as opposed to an increase in CVP). Feissel et al were able to demonstrate that in mechanically ventilated patients in septic shock, an IVC variation of 12% or more identified patients that were likely to respond to a colloid bolus (with a CO increase of 15% or more). Therefore, while a 50% collapse can be used in patients that are breathing spontaneously, a 12% collapse is a more reliable threshold for administration of fluids in mechanically ventilated patients.
**PEARL: Look for an IVC collapse of ≥ 50% as indicator of low CVP. In mechanically ventilated patients, a respiratory variation of ≥ 12% can help identify patients that are likely to respond to a fluid bolus.
Nagdev AD, Merchant RC, Tirado-Gonzalez A, et al. Emergency Department Bedside Ultrasonographic Measurement of the Caval Index for Noninvasive Determination of Low Central Venous Pressure. Ann Emerg Med. 2010;55(3):290-5.
Feissel M, Michard FDR, Faller JP, et al. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004;30(9):1834-7.
3) Pulse Pressure Variation (∆PP) and Systolic Pressure Variation (SPV):
The pulse pressure and systolic pressure show slight variations with respiration that are mostly caused by increased blood return to the right heart with the negative pressure generated during inspiration. These variations are exacerbated by hypovolemia and the measurement of these variations beyond a certain threshold can be used as an indicator of fluid responsiveness.
How to do it: ∆PP and SPV have been shown to reliably predict fluid responsiveness in patients with an established arterial catheter that are mechanically ventilated and not making a breathing effort. The patients should also be in sinus rhythm as arrhythmias, and particularly atrial fibrillation, can affect their interpretation. The blood pressure tracing will need to be slowed down in order to better observe the blood pressure variation with respiration (see Figure 1). Calculating the variation in pulse pressure and systolic pressure will be done in a similar way as was previously done for the CVP:
ΔPP = (PPMAX - PPMIN) / [(PPMAX + PPMIN) / 2] x 100%
PPMAX = maximal pulse pressure, PPMIN = minimal pulse pressure (see Figure 4).
SPV = (SPMAX - SPMIN) / [(SPMAX + SPMIN) / 2] x 100%
SPMAX = maximal systolic pressure, SPMIN = minimal systolic pressure (see Figure 3).
How to interpret the numbers: a ∆PP of 11% or more and an SPV of 15% or more are indicative that the patient will likely respond to fluids.
How to do it: ∆PP and SPV have been shown to reliably predict fluid responsiveness in patients with an established arterial catheter that are mechanically ventilated and not making a breathing effort. The patients should also be in sinus rhythm as arrhythmias, and particularly atrial fibrillation, can affect their interpretation. The blood pressure tracing will need to be slowed down in order to better observe the blood pressure variation with respiration (see Figure 1). Calculating the variation in pulse pressure and systolic pressure will be done in a similar way as was previously done for the CVP:
ΔPP = (PPMAX - PPMIN) / [(PPMAX + PPMIN) / 2] x 100%
PPMAX = maximal pulse pressure, PPMIN = minimal pulse pressure (see Figure 4).
SPV = (SPMAX - SPMIN) / [(SPMAX + SPMIN) / 2] x 100%
SPMAX = maximal systolic pressure, SPMIN = minimal systolic pressure (see Figure 3).
How to interpret the numbers: a ∆PP of 11% or more and an SPV of 15% or more are indicative that the patient will likely respond to fluids.
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| Figure 1: Blood pressure variation with respiration. |
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Figure 4 in Gunn et al., 2001: Pulse pressure variation.
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| Figure 3 in Gunn et al., 2001: Systolic pressure variation. |
**PEARL: In mechanically ventilated patients in sinus rhythm, a ∆PP ≥ 11% or a SPV ≥ 15% or more are good predictors of fluid responsiveness.
Marik PE, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature. Crit Care Med. 2009;37(9):2642–2647.
4) Brachial Artery Peak Velocity Variation (∆V):
This concept is similar to the systolic pressure variation method described above, but with the advantage of being non-invasive. While interesting and promising, it is important to mention that only a couple studies investigating this technique were performed to date.
How to do it: To determine the change in brachial artery peak velocity, the ultrasound in placed in doppler mode over the brachial artery (see picture) of an intubated and ventilated patient. It offers a dynamic parameter of fluid responsiveness that is calculated similarly to SPV using the following formula:
ΔV = (VMAX − VMIN) / [(VMAX + VMIN) / 2] x 100%
VMAX = maximal velocity, VMIN = minimal velocity (see Figure 2).
VMAX = maximal velocity, VMIN = minimal velocity (see Figure 2).
How to interpret the numbers: The study by Monge Garcia et al reported that a change in peak velocity of more than 10% predicted fluid responsiveness with a sensitivity of 74% and a specificity of 95%.
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| Placement of probe for brachial artery ultrasound. |
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| Figure 2 in Monge Garcia et al., 2009: "...Doppler evaluation of brachial artery peak velocity variation in a responder patient and nonresponder patient". |
**PEARL: This technique is a non invasive variant of SPV and can be useful when an arterial line cannot be established. A respiratory variation > 10% can be used to guide additional fluid administration.
5) Passive Leg Raising (PLR):
How to do it: This technique has been described and validated in a number of studies. The patient is initially in a semi-recumbent position, then placed supine followed by elevation of the legs by health care workers to an angle of 45 degrees. Alternatively, the legs can be raised to an angle of 90 degrees both at the hips and knees. Blood contained in the venous system of the lower extremities is transferred to the intrathoracic compartment resulting in an increased cardiac preload which then translates into an increased cardiac output. This can be performed in both spontaneously breathing and ventilated patients, as well as patients with arrhythmias.
How to interpret the numbers: In patients with an established arterial catheter, a 10-15% increase in the arterial pulse pressure or systolic pressure would indicate that the patient is preload dependent and will likely respond to fluid administration. The advantage of this technique over fluid challenges is that it relies on the shifting of blood that is already located in the intravascular space and is therefore unlikely to result in pulmonary edema.
How to interpret the numbers: In patients with an established arterial catheter, a 10-15% increase in the arterial pulse pressure or systolic pressure would indicate that the patient is preload dependent and will likely respond to fluid administration. The advantage of this technique over fluid challenges is that it relies on the shifting of blood that is already located in the intravascular space and is therefore unlikely to result in pulmonary edema.
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| Figure 4 in Marik et al., 2011: Passive leg raising. |
**PEARL: Passive leg raising results in the transfer of 250 to 750ml of blood to the thoracic compartment. In the event an arterial catheter cannot be established, simply observing an increase in blood pressure by cuff pressure measurement can be an indication that the patient will benefit from additional fluid administration.
Alternative to ScvO2 Measurement:
Central lines terminating in the superior vena cava (i.e. internal jugular and subclavian placement) can also be used to determine the central venous oxygenation (ScvO2), as part of the EGDT protocol. An ScvO2 of less than 70% would be an indicator that oxygen delivery to tissues is not matching the demand, and that further interventions are needed such as: 1) Intubation to increase PaO2, 2) Blood transfusion to achieve a Hct of ≥ 30%, 3) Initiation of an inotrope, usually Dobutamine. While ScvO2 was shown to correlate with mixed venous oxygenation SvO2 obtained from a pulmonary artery catheter, peripheral venous blood gases (VBG) are not good indicators of systemic oxygen extraction.
Lactic acid has recently gained interest as a possible substitute for ScvO2 to determine adequate delivery of oxygen to tissues. A study by Jones et al has shown that a lactic acid clearance of more than 10% at least two hours after adequate fluid resuscitation was non inferior to an ScvO2 goal of ≥70%. Lactic acid can therefore be used in place of ScvO2, with the advantage that it can be easily drawn from a peripheral vein.
Peripheral Delivery of Pressors and Inotropes:
Finally, central lines offer good vascular access for the infusion of pressors and inotropes. It is important to mention that central access is preferred for infusion of those medications because of the concern for peripheral vascular and tissue damage. The problem with pressors delivered peripherally is with infiltration. A long peripheral IV placed in a good vein could certainly be used to deliver pressors but the risk of skin necrosis and its implications (infection, need for grafting) is just too high. Some institutions however have been using more dilute formulations of certain pressors for peripheral use. There is no data supporting this but institutional records have shown it to be safe. Please keep in mind you should make sure to stay within your institution’s guidelines for the use of pressors. Your pharmacy needs to be on board with this as they are responsible for mixing/diluting the meds and dispensing them. The dilution would also have to be compatible with pump presets and can therefore change from institution to institution. Here are a few examples of formulations currently in use.
- Norepinephrine 8mg/250mL D5W/NS (Central)
- Norepinephrine 4mg/250mL D5W/NS (Peripheral)
- Epinephrine 4mg/250mL D5W/NS (Central)
- Epinephrine 1mg/250mL D5W/NS (Peripheral)
- Phenylephrine 80mg/250mL D5W/NS (Central)
- Phenylephrine 10mg/250mL D5W/NS (Peripheral)
- Vasopressin 40units/250mL D5W/NS (Central)
- Vasopressin 20units/250mL D5W/NS (Peripheral)
- Dopamine 800mg/250mL D5W/NS (Central)
- Dopamine 400mg/250mL D5W/NS (Peripheral)
- Dobutamine 1000mg/250mL D5W/NS (Central)
- Dobutamine 500mg/250mL D5W/NS (Peripheral)
- Milrinone 40mg/100mL D5W/NS (Central)
- Milrinone 20mg/100mL D5W/NS (Peripheral)
Other References:
Marik PE, Monnet X, and Teboul JL. (2011). Hemodynamic parameters to guide fluid therapy. Ann Intensive Care. 2011;21;1(1):1.
Preisman S. Predicting fluid responsiveness in patients undergoing cardiac surgery: functional haemodynamic parameters including the Respiratory Systolic Variation Test and static preload indicators. Br J Anaesth. 2005;95(6):746–755.
Very Helpful, thank you
ReplyDeleteVery useful overview, and great article links. I'm looking forward to trying the brachial artery doppler trick. Thanks.
ReplyDeleteHappy you enjoyed it. I really like your blog by the way!
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