Correspondence
Elevation of Systemic Oxygen Delivery in the Treatment of Critically Ill Patients
N Engl J Med 1994; 331:1160-1162October 27, 1994
- Article
To the Editor:
The study by Hayes et al. (June 16 issue)1 demonstrates that excessive doses of adrenergic agents (dobutamine alone or in combination with norepinephrine) may result in altered tissue function and increased mortality rates among critically ill patients. One should not infer from this study, however, that dobutamine should be avoided as a means of increasing oxygen delivery in some groups of critically ill patients or that attempts to optimize oxygen delivery in relation to the metabolic demands of the critically ill should be discouraged.
Two important issues must be considered. First, even though nearly half the patients included in the study by Hayes et al. were described as having septic shock, the blood lactate levels were not very elevated (2.1 to 2.2 mmol per liter), and no sign of the dependency of oxygen uptake on oxygen delivery was documented. Thus, the rationale and need for further increases in oxygen delivery can be seriously questioned.2,3 Second, as the authors acknowledge, the administration of fluids was less aggressive in this trial than in other trials.4 In fact, fluid administration may have been insufficient in the study by Hayes et al., resulting in the excessive requirements for adrenergic agents in their patients. The doses of dobutamine, which were already quite substantial (median maximal dose, 10 μg per kilogram of body weight per minute) in the control group, were phenomenal (median maximal dose, 25 μg per kilogram per minute) in the treatment group. Indeed, the highest dose of dobutamine was 200 μg per kilogram per minute in both groups. The usual dose ranges from 2.5 to 15 μg per kilogram per minute, and a dose of 5 μg per kilogram per minute often results in a substantial increase in oxygen delivery in patients with septic shock.3,5 Similarly, the doses of norepinephrine were excessive and may well have caused inappropriate vasoconstriction and the subsequent development of multiple-organ failure.
The article by Hayes et al. reemphasizes that fact that adrenergic agents are no substitute for fluid administration and that such agents may have deleterious effects when administered at doses that are not recommended. Nevertheless, these observations should not detract from the necessity of maintaining oxygen delivery at optimal levels in critically ill patients. Rather than aim at achieving arbitrary target values in all patients, we believe that this process should be based on a careful clinical evaluation of the individual patient, complemented by measurements of cardiac output, determinations of mixed venous oxygen saturation (or the oxygen-extraction ratio), and other measurements of tissue perfusion, such as the base deficit, blood lactate level, or gastric intramucosal pH.
5 ReferencesJean-Louis Vincent, M.D., Ph.D.
David J. Bihari, F.R.C.P.
Hopital Erasme, B-1070 Brussels, Belgium1
Hayes MA ,Timmins AC ,Yau EHS ,Palazzo M ,Hinds CJ ,Watson D . Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994;330:1717-1722
Full Text | Web of Science | Medline2
Bihari D ,Smithies M ,Gimson A ,Tinker J . The effect of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 1987;317:397-403
Full Text | Web of Science | Medline3
Vincent JL ,Roman A ,DeBacker D ,Kahn RJ . Oxygen uptake/supply dependency: effects of short-term dobutamine infusion. Am Rev Respir Dis 1990;142:2-7
Web of Science | Medline4
Shoemaker WC ,Kram HB ,Appel PL ,Fleming AW . The efficacy of central venous and pulmonary artery catheters and therapy based upon them in reducing mortality and morbidity. Arch Surg 1990;125:1332-1338
Web of Science | Medline5
Vincent JL ,Roman A ,Kahn RJ . Dobutamine administration in septic shock: addition to a standard protocol. Crit Care Med 1990;18:689-693
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To the Editor:
Megadoses of catecholamines will not only cause alterations in regional blood flow but also stress the heart to a maximal degree. There are suggestions in the literature that high doses of dobutamine may be associated with increased mortality in patients with cardiogenic shock.1 Cardiocirculatory failure may thus be viewed as a direct consequence of iatrogenic intervention.
In rare cases, rescue treatment with doses of dobutamine as high as 200 μg per kilogram per minute and doses of norepinephrine as high as 20 μg per kilogram per minute may be tried for short periods in critically ill patients with cardiogenic shock. From our viewpoint as experienced clinicians, however, it seems unwise to include such tremendously high doses of catecholamines in a controlled study of patients when the aim is to increase systemic oxygen delivery.
1 ReferencesHubert Bohrer, M.D.
Heinfried Schmidt, M.D.
Alfons Bach, M.D.
University of Heidelberg, 69120 Heidelberg, Germany1
Moulopoulos SD ,Stamateolopoulos SF ,Nanas JN ,Kontoyannis DA ,Nanas SN . Effect of protracted dobutamine infusion on survival of patients in cardiogenic shock treated with intraaortic balloon pumping. Chest 1993;103:248-252
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To the Editor:
Hayes et al. prospectively studied a series of patients at high risk admitted to the intensive care unit at variable periods after surgery or after the onset of medical illnesses. The Acute Physiology and Chronic Health Evaluation (APACHE) II and III scores and the incidence of organ failure at the time of admission to the intensive care unit and before the beginning of the study suggest that these patients may have been at a rather late stage in the course of their disease. This view is supported by the observation that the authors were unable to achieve the optimal goals in 35 of the 50 patients in the treatment group, but of the 33 patients in whom target values for cardiac index and oxygen delivery and consumption were achieved, 31 survived.
Hayes et al. indicate that they were following our protocol. However, our protocol was designed to prevent tissue hypoxia by the use of prophylactic or early aggressive therapy (8 to 12 hours postoperatively).1 We decided on this approach after our first study, in which about one third of our patients who started the protocol several days after surgery had only marginal improvement.
The importance of early therapy was pointed out in an editorial2 accompanying the first paper on this subject by Hayes et al. That tissue hypoxia and oxygen debt can be corrected in the early, reversible stage has been clearly demonstrated; the data of Hayes et al. suggest that there comes a time when this problem is no longer reversible.
2 ReferencesWilliam C. Shoemaker, M.D.
Paul L. Appel, M.P.A.
King-Drew Medical Center, Los Angeles, CA 900591
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;94:1176-1186
CrossRef | Web of Science | Medline2
Shoemaker WC . A stitch in time saves lives. Chest 1993;103:663-664
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Author/Editor Response
The authors reply:
To the Editor: We agree with Shoemaker and Appel that it is essential to institute therapy early during critical illness and accept their point that refractory tissue hypoxia may already have developed in some of our patients. Postoperative initiation of therapy is nevertheless still typical clinical practice in numerous institutions, and a delay after the initial insult is often unavoidable in many critically ill patients, such as those with acute respiratory failure or septic shock. It is also difficult to reconcile Shoemaker and Appel's concern with Vincent and Bihari's suggestion that the patients may not have been sick enough to require further increases in oxygen delivery. Determining individual requirements for such treatment is complicated by the controversy surrounding current methods for evaluating tissue hypoxia.1
Vincent and Bihari's claim that our approach to fluid resuscitation was less aggressive than that of others suggests that they may have misinterpreted our paper. We randomized only patients in whom target values were not achieved in response to optimal volume replacement, assessed as the pulmonary-artery occlusion pressure at the plateau value for left ventricular stroke work, and optimal filling pressure was reestimated frequently. We contend that this approach constitutes aggressive controlled volume replacement.
The choice and doses of dobutamine and norepinephrine were based on a published study suggesting that these agents may improve the outcome in patients with septic shock.2 At the time our study was conceived, these agents, in these doses, were being widely recommended as the best means of consistently increasing oxygen delivery and consumption3 and were being promoted for use in heterogeneous groups of patients at high risk. We must emphasize that the highest doses of dobutamine in the treatment group were used only if they increased oxygen consumption without clinically apparent adverse effects. Otherwise, the dobutamine infusion was titrated to the lowest dose that achieved the highest possible oxygen delivery and consumption. In the light of previous recommendations,3 we would almost certainly have been criticized if we had not made an aggressive attempt to increase oxygen consumption in the treatment group. We agree that treatment with inotropic agents that is more precisely tailored to the individual patient may be more effective, although this has yet to be clearly demonstrated.
Finally, we believe that the fact that 31 of the 33 patients in whom target values were achieved survived is consistent with our view, shared by others,4 that the response of oxygen delivery and consumption to treatment provides an excellent indication of the physiologic reserve and therefore of the prognosis.
4 ReferencesMichelle A. Hayes, F.R.C.A.
St. Bartholomew's Hospital, London EC1A 7BE, United KingdomMark Palazzo, F.R.C.A.
Charing Cross Hospital, London W6 8RB, United KingdomCharles J. Hinds, F.R.C.A.
David Watson, B.Sc., F.R.C.A.
St. Bartholomew's Hospital, London EC1A 7BE, United Kingdom1
Pinsky MR. Oxygen delivery and uptake in septic patients. In: Vincent JL, ed. Yearbook of intensive and emergency medicine. Berlin, Germany: Springer-Verlag, 1993:373-84.
2
Edwards JD ,Brown GCS ,Nightingale P ,Slater RM ,Faragher EB . Use of survivors' cardiorespiratory values as therapeutic goals in septic shock. Crit Care Med 1989;17:1098-1103
CrossRef | Web of Science | Medline3
Edwards JD ,Nightingale P . Use of survivors' cardiorespiratory values as therapeutic goals in septic shock. Crit Care Med 1991;19:127-127
CrossRef | Web of Science | Medline4
Vallet B ,Chopin C ,Curtis SE , et al. Prognostic value of the dobutamine test in patients with sepsis syndrome and normal lactate values: a prospective, multicenter study. Crit Care Med 1993;21:1868-1875
CrossRef | Web of Science | Medline
- Citing Articles (5)
Citing Articles
1
Justin Woods, Andrew Rhodes. 2010. Care of the High Risk Patient Undergoing Surgery. , 154-166.
CrossRef2
Michael O???Leary, Michael Davis, David Bihari. (1999) Myocardial protection in the intensive care unit. Current Opinion in Critical Care 5:5, 400-407
CrossRef3
J VINCENT. (1996) DETERMINATION OF OXYGEN DELIVERY AND CONSUMPTION VERSUS CARDIAC INDEX AND OXYGEN EXTRACTION RATIO. Critical Care Clinics 12:4, 995-1006
CrossRef4
K KELLY. (1996) DOES INCREASING OXYGEN DELIVERY IMPROVE OUTCOME? YES. Critical Care Clinics 12:3, 635-644
CrossRef5
J.-L. VINCENT, D. BACKER. (1995) Oxygen uptake/oxygen supply dependency: Fact or fiction?. Acta Anaesthesiologica Scandinavica 39, 229-237
CrossRef
