Patient Outcomes
J. Wilson, M. Cecconi, and A. Rhodes
Introduction
Hemodynamics is the physiology concerned with movements of blood and the forces involved in the circulation [1]. Hemodynamic monitoring involves the study of this physiology, with various forms of technology to understand these forces and the movement of blood, and put them into a clinical context that can be assessed and used to direct therapy. The main function of these hemodynamic forces is to transport substrates to, and clear metabolites from, the cells in order to allow ade- quate cellular function. The assessment of hemodynamics must, therefore, also take into account the metabolic status of the cell in particular in relation to its supply of oxygen. A relative lack of oxygen at the cellular level is known as tissue hypoxia. The identification and correction of tissue hypoxia remains one of the central facets of any protocol that aims to resuscitate patients from shock conditions. This is because tissue hypoxia has both pathological relevance in vitro [2] and an association with poor outcome [3]. When monitoring the circulation, therefore, an estimate must be made of the adequacy of the circulation with respect to the likelihood of there being underlying tissue hypoxia. With most currently available monitors for routine prac- tice it is impossible to assess tissue hypoxia at either a local or a cellular level. An extrapolation is, therefore, made from a number of globally measured parameters that can provide an estimate of the likelihood of underlying disturbance. Clinicians can then use this information to direct therapeutic decisions in order to benefit their patients.
Key Variables that are Measured
Resuscitation from shock always entails attempting to increase a patient’s tissue oxy- gen delivery (DO2) to an amount that is considered appropriate to reverse the shock by alleviating tissue hypoxia and ensuring aerobic respiration at the tissue level.
This theory is supported by a number of observations that demonstrate that acutely ill patients often have a level of oxygen utilization that is pathologically dependent on their DO2[4]. Any reduction in DO2leads to a further reduction in oxygen con- sumption and, therefore, tissue hypoxia. Resuscitation protocols are, therefore, aimed at increasing DO2to a level whereby tissue hypoxia disappears and cellular function returns to normal. The key component of DO2is the cardiac output. Many hemodynamic monitors, therefore, contain the technology to measure and monitor cardiac output and or its key determinants – stroke volume and heart rate. At the bedside, these variables are then manipulated to levels that have either been prede-
termined to be associated with a good outcome [5 – 6] or more often to a situation where the patient’s clinical condition is improving on an individualized basis [7].
Key Concepts
There are a number of tests that have been described for the effective use of invasive hemodynamic monitoring procedures and these revolve around two main princi- ples. First, is the measurement of the physiological variable reproducibly accurate, and second, if the physiological variable is known, can knowledge of that measure- ment be used to improve outcome in the patient population [8 – 9]? Thus, these tests must include answers to the following questions to be of value in treating sick patients:
1. The information received improves the accuracy of diagnosis, prognosis, and/or treatment based on known physiological principles.
2. The parameter can be reliably and safely measured under typical conditions.
3. The information received cannot be acquired from less invasive and less risky monitoring.
4. Interventions exist that can influence the monitored variable.
5. The changes in diagnosis and /or treatment result in improved patient out- comes (morbidity and mortality).
6. The changes in diagnosis and /or treatment result in more effective use of health care resources.
These tests can be combined to provide us with a number of key concepts that are of utmost importance when evaluating the differing technologies available for hemodynamic monitoring.
) Primum non nocere (first do no harm). Whichever technology or modality of monitoring the circulation is used, safety of the patient should be paramount.
The use of monitoring should not add to the burden of morbidity suffered by the patient.
) The type of monitoring is dependent on the environment in which it is to be used. The invasiveness or sophistication of any given monitoring device must be tailored to the clinical environment. Although pulmonary artery catheteriza- tion may be reliably performed in the operating room or the intensive care unit (ICU), it is not so easily performed in the ward or emergency room setting.
) Hemodynamic monitoring should be undertaken at a time when clinical out- comes can be influenced. Prevention is better than cure. Improving carriage of oxygen to the cells is important before irreversible cell damage has occurred. Once irreversible cell damage has occurred then, no matter how much DO2is increased, published evidence suggests that further benefit will not accrue [6, 7].
) No monitoring therapy will improve any patient outcome unless linked to a relevant clinical protocol or therapeutic target. This is especially important as many clinical studies have demonstrated that the use of hemodynamic monitor- ing without an associated protocol has no benefit to patient outcomes [10 – 12], while studies assessing treatment protocols early on in disease processes have demonstrated efficacy in terms of reducing both morbidity and mortality [5 – 7]. Clinicians must be aware that the use of invasive monitoring equipment
will always carry the potential risk of harm to the patient and that they are thus duty bound to ensure that the monitoring equipment is used to direct therapy.
) Avoidance of circutrauma. There are many examples cited in the literature where overzealous use of logical and physiologically intuitive treatment strate- gies has ultimately been shown to be detrimental [13]. It is important not to follow the same path with hemodynamic monitoring and resuscitation. Care must be taken as over enthusiastic resuscitation has the potential to cause harm [14] but at the same time inadequate resuscitation may lead to the demise of the patient. The monitored variables should be used in a fashion that is proven to cause benefit [15]. It is important to realize that rational use of these tools can limit resuscitation as well as promoting it. It is possible to cause pulmonary edema with the overuse of intravenous fluids without some form of break that can be achieved by the sensible monitoring of preload, just as easily as it is to allow hypovolemia with tissue hypoxia from inadequate resuscitation.
Available Technologies
Central Venous Pressure Monitoring
The central venous pressure (CVP) is often used a marker of preload. In this respect it is used as an estimate of right atrial pressure (RAP). The RAP approximates to the right ventricular end-diastolic pressure (RVEDP) which is related through the ven- tricular compliance to the end-diastolic volume (EDV). Consequently, it is important to understand the relationship between EDP and EDV. In patients with normal ven- tricular compliance, an initial increase in EDV will not alter the EDP until a certain point. After that point, the increase in volume is coupled to an increase in pressure.
Patients with decreased compliance have their ventricular function curve shifted to the left. It is difficult to determine this compliance clinically. Fluid challenges can be used to help differentiate between patients with low preload and low compliance and patients with high preload and normal compliance. In patients with a low preload, a fluid challenge will not alter the CVP reading or it may do for just a few minutes but then will rapidly return to the pre-fluid infusion state. Patients with a high pre- load and normal compliance will dramatically increase the CVP reading in response to the same fluid challenge. Isolated values of CVP are of limited value as compli- ance varies both from patient to patient and with time in the same patient. Despite the low specificity of CVP to accurately delineate preload, it can be used to help assess the fluid status of patients by assessing the response to a fluid challenge.
The Pulmonary Artery Catheter
The pulmonary artery catheter (PAC) is currently the gold standard method of mon- itoring of circulatory dysfunction. It was first described as a diagnostic tool in 1945 and was introduced to clinical practice following the work of Swan and Ganz in the 1970s. The catheter allows measurement of RAP, mean pulmonary artery pressure (MPAP), the pulmonary artery occlusion pressure (PAOP), the cardiac output, and the mixed venous oxygen saturation (SvO2) which is a measure of the balance between oxygen supply and demand. The left ventricular end-diastolic pressure (LVEDP) can be estimated from the PAOP [16], which can be used to help assess the volume status of the patient.
The catheter estimates the cardiac output using the thermodilution technique.
Injection of a cold fluid bolus into the right atrium results in a transient decrease in the blood temperature in the pulmonary artery, which is sensed by a thermistor at the tip of the catheter. The mean temperature reduction is inversely proportional to the cardiac output (derived from the modified Stewart Hamilton equation). Modern technologies allow this to be performed on a continuous basis by the utilization of a warming coil attached to the PAC. New fast acting thermistors in the tip of the PAC allow continuous assessment of the RVEDV and ejection fraction. A major criticism of the use of PAC is the labor-intensive nature of use, which requires access to a large vein (internal jugular, subclavian or femoral) through which a catheter sheath is introduced using the Seldinger technique. The catheter, with a 1.5 cm distal balloon, is advanced through the sheath and floated through the right atrium, right ventricle, into the pulmonary artery, and then finally into the wedged position. Continuous monitoring of pulmonary artery or wedge pressure during this procedure ensures correct positioning of the catheter. There is a suggestion that because of this inser- tion technique, the PAC is overly invasive and may complicate patients’ clinical course.
Arterial Pulse Pressure Techniques
The history of pulse contour techniques dates back more than 100 years and is based on obtaining continuous cardiac output by the analysis of the arterial waveform. In 1899, Otto Frank developed the Windkessel (air chamber) model to simulate the heart-vessels interaction [17]. This model comprised a circuit in which fluid was pumped in tubes through chambers. The tubes were completely fluid-filled but the chambers contained some air. As the fluid was not compressible, the behavior of the air was thought to mimic aortic distension, or compliance, in blood vessels. Frank also deduced that the stroke volume could be calculated from the change in pres- sure. In 1904, Erlanger and Hooker proposed a correlation between stroke volume and change in arterial pressure and suggested there was a correlation between car- diac output and the arterial pulse contour [18]. This eventually led to the develop- ment of algorithms relating the arterial pulse contour and cardiac output; only with the recent advent of computer technology has it been possible to develop these algo- rithms to a level useful for clinical practice. These technologies offer the ability to monitor cardiac output (and, therefore, stroke volume) on a near real time basis.
They do so by extracting data from arterial pressure lines, which are routinely used in the critically ill population. They are, therefore, described as minimally invasive devices when compared to the PAC. There are at present four companies marketing technologies that utilize these principles for the measurement and monitoring of cardiac output. Each of these technologies has distinct differences from its competi- tors which must be understood before being able to fully evaluate the device. What is consistent for all these devices, however, is the recognition that accurate data only comes from appropriate use of arterial pressure lines. If the arterial trace is damped or hyperresonant, then meaningless data will be derived [19]. A novel and poten- tially interesting by-product of these new devices is the ability to get volumetric information regarding the pre-load status of the patient. By analyzing the kinetics of the thermo/indicator-dilution curve, additional parameters can be derived that may enable clinicians to better understand the volemic state of their patients. Although of interest, these variables have yet to be rigorously tested in clinical trials to prove their efficacy in terms of improving relevant patient outcomes.
Other Minimally Invasive Devices for the Measurement of Cardiac Output
There are a variety of other technologies that are marketed for the monitoring of cardiac output. These include techniques that utilize the Doppler theory [20], the Fick principle through the re-breathing of carbon dioxide [21], or bio-impedance techniques [22]. The most popular of these techniques seem to be the technologies that utilize the Doppler theorem to assess blood velocity and, therefore, flow. This technique can be performed either from a suprasternal or a transesophageal route.The Doppler sensor can be shone across the aorta (either the arch or the descending portions) to assess blood velocity. This measure can then be changed to flow by cor- recting for aortic cross sectional area (either measured or calculated via an algo- rithm). All of these techniques have been validated to a certain extent in specific clinical situations, although their validity in all clinical environments is not as robust as with the previously described technologies.
Evidence Based Practice for the Use of Hemodynamic Monitoring
An appraisal of the current evidence for hemodynamic monitoring needs to focus on three main areas. The first is whether there are any data either for or against hemodynamic monitoring in the critically ill patient; the second area is whether there is any guidance to help us choose between different technologies; and the third area is surrounding the use of these devices within goal-directed therapies.
Evidence for or against Hemodynamic Monitoring
Much of the available evidence for or against hemodynamic monitoring is based around the PAC. Intuitively clinicians assumed that the extra information provided by this device would enable them to improve outcome for their patients; however, a number of observational studies suggested that the use of the PAC was associated with a worsening outcome [15, 23, 24]. There have now been three randomized con- trolled studies assessing this question [10 – 12]. All have been on a limited number of patients with the hypothesis being to study whether the PAC (without an associ- ated treatment algorithm) has any influence on mortality. The answer in each of these studies was that the use of the PAC, without using it to target specific thera- peutic endpoints, conferred no benefit to the patient. Conversely the opposite was also noted: that the use of the PAC did not confer any disadvantage to the patients.
The salient point from all of these studies was the understanding that a monitoring technology, on its own, will seldom influence patient outcome (either beneficially or detrimentally). It is more important to use the information correctly in an evidence based protocol (see later). It is also possible that the use of these devices may limit resuscitation and, therefore, prevent deleterious or potentially injurious therapies being administered to patients. This, however, is very difficult to study and has never been (and may never be) proven.
Evidence For or Against an Individual Technology
There is a plethora of data describing the validation of individual hemodynamic monitors. It is beyond the scope of this article to go into all of these papers, but suf- fice to say, it is vitally important to understand how and when each device works
and the problems and pitfalls of each tool. It is also worth noting that the validation studies have all been performed in a tightly controlled research setting, and it is highly unlikely that any device will perform to the same level of accuracy in the uncontrolled clinical environment [25].There is only one study in the literature that has randomized patients between differing technologies [12]. The UK PAC-Man study randomized 802 patients to either receive the PAC or any other form of cardiac output monitoring. There was no significant differences in morbidity or mortality between these two groups (hazard ratio 10.6, 95 % confidence intervals 0.9 – 1.26).
This suggests that if cardiac output is to be used in a clinical protocol it is probably less important how it is measured than how it is used.
Goal-Directed Use of Cardiac Output Monitoring Technologies
There are many studies assessing clinical protocols in the context of randomized controlled trials. Most of these have shown utility and improved outcome for patients [5 – 7], a few have shown no effect [26], and only one has shown harm [14]
(Table 1). Furthermore with all of these studies it is very important to note that the outcome was dependent on the early recognition by clinicians of tissue hypoxia developing in their patients and the use of cardiovascular monitoring to target goal- directed therapy. In the study where the goal-directed therapy caused harm [14], the patients were admitted to the ICU long after tissue hypoxia had progressed to tissue death and the patients were then over enthusiastically treated with extremely large doses of dobutamine. The poor outcome was perhaps inevitable and was not caused by the monitoring technique but by the lateness in instituting therapy in this criti-
Table 1. Studies assessing clinical protocols of goal-directed therapy in randomized controlled trials.
Year Author Patients When Target Where
1993 Boyd [5] Shoemaker high risk surgical criteria
Preoperative until 24 hours after surgery
DO2I 8 600 ml/min/m2 ICU
1994 Hayes [14] Established critically ill Shoemaker high risk surgical criteria, sepsis, respiratory failure, trauma
Within 24 hours of admission
CI 8 4.5 l/min/m2, DO2I 8 600 ml/min/m2, VO2I 8 170 ml/min/m2
ICU
1995 Gattinoni [26]
Shoemaker high risk surgical criteria, sepsis, respiratory failure, trauma
Within 48 hours for 5 days
CI 8 4.5 l/min/m2or SvO2 8 70 %
ICU
2001 Rivers [7] Severe sepsis and septic shock
On admission for 6 hours before ICU admission
ScvO2 8 70 %, CVP 8 – 12 mmHg, MAP 8 65 mmHg, Hct 8 30 %
ER
2005 Pearse [6] High risk surgical patients Immediately after surgery for 8 hours protocol
DO2I 8 600 ml/min/m2 ICU
DO2I: oxygen delivery index; CI: cardiac index; VO2I: oxygen consumption index; SvO2: mixed venous oxygen saturation; ScvO2: central venous oxygen saturation; CVP: central venous pressure; MAP: mean arterial pres- sure; Hct: hematocrit; ICU: intensive care unit; ER: emergency room
cally ill group of patients. It is important to recognize that all of these protocols are not technology specific. It is the measured variable that is being targeted that is important in the context of a specific disease setting. Although it has not been stud- ied, it is highly likely that any validated technology that works in that environment, could have been used to direct the therapy with the same beneficial effects.
Conclusion
Hemodynamic monitoring has evolved considerably over the last 30 years. It is now widely accepted that bedside clinical examination and routine hemodynamic obser- vations are not sufficient to evaluate the adequacy of either resuscitation or the met- abolic status of a patient. These monitoring tools allow us to understand the physiol- ogy of the circulation at the bedside and, thereby, to direct therapies appropriately.
It beholds us to use the information we get in a sensible, and where available, an evi- denced based way. Doubts concerning the use of the PAC have driven the develop- ment of newer less invasive devices. These devices can be as accurate as the PAC and are often easier to use. This does not necessarily mean they are better than the old technology, though, and clinical utility does require outcome based studies to be performed. Many of the newer devices offer exciting and novel new variables that could be targeted as endpoints for resuscitation. Before there are good data to sup- port this practice, however, much caution should be advocated. The most important point to recognize about modern hemodynamic monitoring, is not that we can mea- sure variables such as cardiac output, it is that we then know what to do with the information. The combined use of appropriate monitoring together with a clinical goal-directed protocol has consistently been shown to improve outcome and is not only beneficial to patients but can also reduce costs and improve the overall utiliza- tion of healthcare resources [6, 27, 28].
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