Experience teaches that to place reliance upon a single sign is precarious. Compare this sign and that, and confident recognition of the patients state grows as these signs group themselves together to form a harmonious picture.
Sir Thomas Lewis1
One of the biggest critical care challenges is a septic patient with massive apparent fluid losses. The losses result from increased capillary permeability and third space sequestration, confounded by reduced vascular tone mediated through induced nitric oxide production, which might be associated with myocardial dysfunction.2 These changes lead to a fall in cardiac output and profound hypotension, which result in poor organ perfusion, multiple organ failure and death. It would probably come as a surprise to most scientists, therefore, that, whereas clinicians have good techniques for measuring cardiac output, there are no easily undertaken bedside methods for measuring total circulating blood volume.
Circulating volume is a major determinant of cardiac output and it has been the response of the latter to fluid challenges that provides us with proxy assessments of circulating volume. Furthermore, it has been the achievement of good cardiac output rather than circulating volume which has consistently been related to better outcomes.37
Given the complex cause of changes in volume, blood pressure and cardiac output in sepsis, how should they be restored? Start by providing large quantities of intravenous fluid (610 litres of crystalloid or 24 litres of colloid) in order to obtain a blood pressure and a hyperdynamic state.8 The type of fluid probably does not matter, but colloids tend to be less likely to cause pulmonary oedema at higher filling pressures.911 Once volume resuscitation is complete, organ perfusion should be restored by increasing blood pressure to pre-morbid values with vasoconstrictors, because organ autoregulation is lost and perfusion becomes pressure dependent.12 Norepinephrine on a full circulation seems to be in favour if dopamine is ineffective or has caused side-effects.13 The resulting improved global circulatory state should provide a sustainable cardiac output for adequate organ function while specific therapies such as timely surgery and antibiotics prevent further insult.
What about the effect of all that fluid on systemic oedema and tissue oxygenation? Systemic oedema is an inevitable late development that follows fluid loading in patients with disturbed tissue permeability. It should not be a distraction to the prime target of achieving a full circulation. Furthermore, the effect of tissue oedema on tissue oxygenation is not necessarily deleterious.14 15
What about haemodynamic targets and monitoring? Use clinical end-points of perfusion in the first instance and insert an arterial line. If cardiac output is low, some measurement of pre-load and cardiac output is appropriate to guide inotrope requirements and avoid cardiac overload.
The foregoing guide sounds simple and should sound familiar. These are some of the latest evidence-based recommendations of the American College of Critical Care Medicine (ACCM) for the treatment of septic shock.16 This excellent document exudes common sense but mostly surprises with its emphasis on clinical assessment in spite of the apparent advantages of technology that allows more and more accurate ways to measure pre-load and cardiac output.
The paper by Stephan and colleagues in this issue therefore comes as a timely reminder that clinical assessment of circulating volume as a first aim to adequate cardiac output in an individual still has a role.17 But how can we seamlessly merge clinical art form and scientific measurement?
The importance of generous volume replenishment in septic shock was first seriously promoted by William Shoemaker and colleagues.4 1821 Shoemakers approach at the time was brave considering that most intensivists were focused on drying patients to improve PaO2 in order to reduce FIO2 to <0.6. Now most would agree that Shoemaker was right. However, when he suggested numerical haemodynamic targets that were subsequently applied prospectively in controlled studies the results were ambiguous.57 22 Where patients did badly the proponents of goal-directed therapy suggested that the targets had been achieved with far too much use of inotropes. Unwittingly, the proponents had struck on the real problem, namely that the targets were population based rather than individually tailored, leading to some patients being driven with inotropes (possibly with insufficient volume) beyond their normal physiological limit. A recent study confirms the importance of physiological reserve for outcome.23
The effect of these studies was to tilt the emphasis towards volume resuscitation and to use inotropes to achieve pre-morbid blood pressure rather than specific oxygen transport targets. Then a spanner was thrown in the works when Connors and colleagues demonstrated that patient management guided by pulmonary artery flotation catheter, the current tool for guiding volume replacement, was associated with a poorer outcome.24 At the time it was thought unlikely that this was due to complications of catheter placement,25 which are relatively low,26 27 but was more related to the way in which the information it provided was used.2831 So, paradoxically, after having been told that our clinical ability to assess haemodynamics is poor,32 33 it seems that clinicians without the flotation catheter get better results.24 Perhaps it is no longer time to ask what is the cardiac output but rather, is cardiac output effective?
How can we define an effective cardiac output (ECO)? The great Paul Wood, doyen of circulatory clinical assessment, firmly established the value of applying Ohms law to bedside assessment and physiological measurement.34 Blood pressure, which is directly related to the product of cardiac output and systemic vascular resistance, if compromised by fluid loss, stimulates sophisticated neuroendocrine compensatory activity. When acute this activity is revealed through clinical signs such as vasoconstriction, tachycardia and sodium retention (oliguria) in order to restore an effective cardiac output and, consequently, blood pressure. Chronic forms of compensated ineffective cardiac output are well recognized in conditions such as cirrhosis, nephrosis and chronic congestive cardiac failure where a sustained state of fluid retention and neuroendocrine activity coexists with a constant risk of organ failure at any further change in circulating volume status.35
An effective cardiac output, on the other hand, should have little need for compensatory mechanisms and individuals should be able to simultaneously have toes that are warm to the touch, and sustain their normal blood pressure preferably with a heart rate below 100 beats min1.36 37 The absolute cardiac output is irrelevant in such circumstances. In the context of critical illness, a reasonable aim for an individual would be to achieve these same clinical end-points with some combination of fluids, vasoactive agent and inotrope. The advantage of clinical end-points for global perfusion is that they remain the same regardless of the phase of illness. The ACCM recommends additional end-points such as urine output and cerebral function; these could be included in a definition of ECO but may be unrelated to global perfusion due to previous established damage. Inevitably, clinical assessment is likely to vary with observer experience and therefore should be used with markers of improving cellular respiration. Furthermore, some patients, particularly those with poor cardiac function, may never reach these end-points; this is perhaps an omen of the likely outcome.
Do clinical end-points mean we can safely abandon all physiological measurement? Almost certainly not.16 Measurements complement clinical assessment but do not replace it. They sometimes provide immediate diagnostic information, can provide confidence to undertake fluid challenges and help monitor trends towards the clinical target. Most significantly, measurement provides us with a language for information exchange. Whereas pulmonary artery catheter data may have been criticised for being poorly acquired, badly used or misleading,38 alternative techniques have not yet been so tainted. Modern continuous methods such as oesophageal Doppler39 40 and thermodilution-calibrated arterial pulse wave contour cardiac output41 are widely used. These techniques might not confirm warm feet from their derived calculations but, when combined with clinical examination, might provide an appropriate numeric target for planning management during that specific phase of the illness.
Improved global perfusion should be associated with improving cellular metabolism. In spite of some well known problems such as lead time bias42 43 and lack of specificity, indicators such as mixed venous oxygen saturation, acid base balance and blood lactate are widely accepted as measures of anaerobic metabolism.16 Progressive acidosis in spite of adequate global perfusion is suggestive of concealed regional ischaemia such as ischaemic hepatitis or bowel infarction. These conditions easily overwhelm buffering capacity and are rarely reversible by further increases in cardiac output. Perhaps the most successful tool for regional perfusion has been gastrointestinal tonometry,44 which with hepatic venous flow and saturation changes4547 might find a niche for monitoring intestinal ischaemia particularly following vasoconstrictor therapy.
So where does the work of Stephan and colleagues17 fit in? They have attempted to correlate clinical indicatorsfour markers of fluid overload and three suggestive of volume losswith measurements of absolute circulating blood volume. They carefully selected stable critically ill patients to minimize confounding variables and defined hypovolaemia as a 10% deviation from expected calculated values for normal circulating blood volume. Their study concluded that a score based on clinical indicators of extracellular volume status reasonably predicted measured circulating hypovolaemia when that loss was approximately 1 litre. The study might be criticised for having some overlap in clinical indicators, using a nomogram as the control for circulating volume or possibly for assuming that a stable vascular compliance allows one to equate absolute circulating volume with effective circulating volume. However, the message is clear: clinical assessment can be reasonably used to indicate volume status.
So might now be the time to apply a similar methodology to assessment of effective cardiac output? A daring start might be to break with tradition and assume this time that physical signs are the gold standard for an individual, and make the measurements in the presence and absence of signs. The volume and inotrope requirements to return to ECO might provide interesting and relevant information, particularly as we embark on outreach critical care.
M. Palazzo
Director of Critical Care
Charing Cross Hospital
London
UK
References
1 Lewis ST. Disease of the Heart, 3rd edn. London: Macmillan and Co., 1942
2 Parrillo JE, Parker MM, Natanson C et al. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 1990; 113: 22742[ISI][Medline]
3 Shoemaker WC. Cardiorespiratory patterns of surviving and nonsurviving postoperative patients. Surg Gynecol Obstet 1972; 134: 8104[ISI][Medline]
4 Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest 1988; 94: 117686[Abstract]
5 Tuchschmidt J, Fried J, Astiz M, Rackow E. Elevation of cardiac output and oxygen delivery improves outcome in septic shock. Chest 1992; 102: 21620[Abstract]
6 Boyd O, Grounds RM, Bennett ED. A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients. J Am Med Assoc 1993; 270: 2699707[Abstract]
7 Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. New Engl J Med 1994; 330: 171722
8 Rackow EC, Kaufman BS, Falk JL, Astiz ME, Weil MH. Hemodynamic response to fluid repletion in patients with septic shock: evidence for early depression of cardiac performance. Circ Shock 1987; 22: 1122[ISI][Medline]
9 Virgilio RW, Rice CL, Smith DE et al. Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study. Surgery 1979; 85: 12939[ISI][Medline]
10 Rackow EC, Falk JL, Fein IA et al. Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock. Crit Care Med 1983; 11: 83950[ISI][Medline]
11 OBrien R, Murdoch J, Kuehn R, Marshall JC. The effect of albumin or crystalloid resuscitation on bacterial translocation and endotoxin absorption following experimental burn injury. J Surg Res 1992; 52: 1616[ISI][Medline]
12 Bersten AD, Holt AW. Vasoactive drugs and the importance of renal perfusion pressure. New Horiz 1995; 3: 65061[Medline]
13 Martin C, Papazian L, Perrin G, Saux P, Gouin F. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993; 103: 182631[Abstract]
14 Baum TD, Wang H, Rothschild HR, Gang DL, Fink MP. Mesenteric oxygen metabolism, ileal mucosal hydrogen ion concentration, and tissue edema after crystalloid or colloid resuscitation in porcine endotoxic shock: comparison of Ringers lactate and 6% hetastarch. Circ Shock 1990; 30: 38597[ISI][Medline]
15 Rackow EC, Astiz ME, Schumer W, Weil MH. Lung and muscle water after crystalloid and colloid infusion in septic rats: effect on oxygen delivery and metabolism. J Lab Clin Med 1989; 113: 1849[ISI][Medline]
16 Task Force of the American College of Critical Care Medicine SoCCM. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med 1999; 27: 63960[ISI][Medline]
17 Stéphan F, Flahault A, Dieudonné N, Hollande J, Paillard F, Bonnet F. Clinical evaluation of circulating blood volume in critically ill patients. Br J Anaesth 2001; 86: 75462
18 Shoemaker WC, Printen KJ, Amato JJ, Monson DO, Carey JS, OConnor K. Hemodynamic patterns after acute anesthetized and unanesthetized trauma. Evaluation of the sequence of changes in cardiac output and derived calculations. Arch Surg 1967; 95: 4929[ISI][Medline]
19 Shoemaker WC. Priorities of resuscitation and subsequent therapy after trauma. N Y State J Med 1972; 72: 194854[ISI][Medline]
20 Shoemaker WC, Montgomery ES, Kaplan E, Elwyn DH. Physiologic patterns in surviving and nonsurviving shock patients. Use of sequential cardiorespiratory variables in defining criteria for therapeutic goals and early warning of death. Arch Surg 1973; 106: 6306[ISI][Medline]
21 Shoemaker WC, Kram HB, Appel PL. Therapy of shock based on pathophysiology, monitoring, and outcome prediction. Crit Care Med 1990; 18: S1925[ISI][Medline]
22 Gattinoni L, Brazzi L, Pelosi P et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. New Engl J Med 1995; 333: 102532
23 Velmahos GC, Demetriades D, Shoemaker WC et al. Endpoints of resuscitation of critically injured patients: normal or supranormal? A prospective randomized trial. Ann Surg 2000; 232: 40918[ISI][Medline]
24 Connors AF, Speroff T, Dawson NV et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. J Am Med Assoc 1996; 276: 88997[Abstract]
25 Soni N. Swan song for the Swan-Ganz catheter? Br Med J 1996; 313: 7634
26 Boyd KD, Thomas SJ, Gold J, Boyd AD. A prospective study of complications of pulmonary artery catheterizations in 500 consecutive patients. Chest 1983; 84: 2459[Abstract]
27 Smart FW, Husserl FE. Complications of flow-directed balloon-tipped catheters. Chest 1990; 97: 2278[Abstract]
28 Iberti TJ, Fischer EP, Leibowitz AB, Panacek EA, Silverstein JH, Albertson TE. A multicenter study of physicians knowledge of the pulmonary artery catheter. Pulmonary Artery Catheter Study Group. J Am Med Assoc 1990; 264: 292832[Abstract]
29 Nadeau S, Noble WH. Misinterpretation of pressure measurements from the pulmonary artery catheter. Can Anaesth Soc J 1986; 33: 35263[ISI][Medline]
30 Gnaegi A, Feihl F, Perret C. Intensive care physicians insufficient knowledge of right-heart catheterization at the bedside: time to act? Crit Care Med 1997; 25: 21320[ISI][Medline]
31 Komadina KH, Schenk DA, LaVeau P, Duncan CA, Chambers SL. Interobserver variability in the interpretation of pulmonary artery catheter pressure tracings. Chest 1991; 100: 164754[Abstract]
32 Rackow EC, Connors AF. Controversies in pulmonary medicine. Invasive measurements are required for assessing hemodynamic status in critically ill patients. Am Rev Respir Dis 1988; 138: 10702[ISI]
33 Eisenberg PR, Jaffe AS, Schuster DP. Clinical evaluation compared to pulmonary artery catheterization in the hemodynamic assessment of critically ill patients. Crit Care Med 1984; 12: 54953[ISI][Medline]
34 Wood P. Diseases of Heart and Circulation, 2nd edn. London: Eyre and Spottiswoode, 1961
35 Rose B. Clinical Physiology of Acid Base and Electrolyte Disorders, 4th edn. New York: McGrawHill Inc., 1994
36 Joly HR, Weil MH. Temperature of the great toe as an indication of the severity of shock. Circulation 1969; 39: 1318[ISI][Medline]
37 Palazzo M, Soni N. Critical-care studies: redefining the rules. Lancet 1998; 352: 13067 [Erratum published in Lancet 1999; 353: 848][ISI][Medline]
38 Gomez CM, Palazzo MG. Pulmonary artery catheterization in anaesthesia and intensive care. Br J Anaesth 1998; 81: 94556
39 Singer M, Bennett ED. Noninvasive optimization of left ventricular filling using esophageal Doppler. Crit Care Med 1991; 19: 11327[ISI][Medline]
40 Singer M, Clarke J, Bennett ED. Continuous hemodynamic monitoring by esophageal Doppler. Crit Care Med 1989; 17: 44752[ISI][Medline]
41 Buhre W, Weyland A, Kazmaier S et al. Comparison of cardiac output assessed by pulse-contour analysis and thermodilution in patients undergoing minimally invasive direct coronary artery bypass grafting. J Cardiothorac Vasc Anesth 1999; 13: 43740[ISI][Medline]
42 Vincent JL, Dufaye P, Berre J, Leeman M, Degaute JP, Kahn RJ. Serial lactate determinations during circulatory shock. Crit Care Med 1983; 11: 44951[ISI][Medline]
43 Falk JL, Rackow EC, Leavy J, Astiz ME, Weil MH. Delayed lactate clearance in patients surviving circulatory shock. Acute Care 1985; 11: 2125[Medline]
44 Fiddian Green RG, Haglund U, Gutierrez G, Shoemaker WC. Goals for the resuscitation of shock. Crit Care Med 1993; 21 (Suppl): S2531
45 Ruokonen E, Soini HO, Parviainen I, Kosonen P, Takala J. Venoarterial CO2 gradient after cardiac surgery: relation to systemic and regional perfusion and oxygen transport. Shock 1997; 8: 33540[ISI][Medline]
46 Ruokonen E, Takala J, Uusaro A. Effect of vasoactive treatment on the relationship between mixed venous and regional oxygen saturation. Crit Care Med 1991; 19: 13659[ISI][Medline]
47 De Backer D, Creteur J, Noordally O, Smail N, Gulbis B, Vincent JL. Does hepato-splanchnic VO2/DO2 dependency exist in critically ill septic patients? Am J Respir Crit Care Med 1998; 157: 121925