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Therapeutics

Increased oxygen delivery reduced morbidity and mortality in high-risk surgery

ACP J Club. 1994 May-June;120:76. doi:10.7326/ACPJC-1994-120-3-076

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Increased oxygen delivery for high-risk surgery


Source Citation

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. JAMA. 1993 Dec 8;270:2699-707.


Abstract

Objective

To determine whether deliberately increased perioperative oxygen delivery reduced mortality and morbidity in patients who were at high risk for both.

Design

Randomized controlled trial lasting 28 days.

Setting

Intensive care unit in England.

Patients

Patients were identified as high risk if they had ≥ 1 of previous severe cardiorespiratory illness, extensive surgery planned for carcinoma, blood loss > 8 U, age > 70 years with limited reserve in ≥ 1 major organ, septicemia, respiratory failure or mechanical ventilation, abdominal catastrophe with hemodynamic instability, acute renal failure, or late-stage aortic disease. The operation had to be planned for or last ≥ 1.5 hours. 107 patients were enrolled (26 after surgery), and all were included in the data analysis.

Intervention

Patients were assigned to a control group (n = 54) receiving standard perioperative care or to a protocol group (n = 53) receiving standard care plus a dopexamine infusion by central vein to achieve oxygen delivery (DO2I) > 600 mL/min per m2 body surface area. The dose started at 0.5 mg/kg body weight per min and was increased until the target DO2I was achieved or adverse cardiovascular effects occurred, to a maximum dose of 8 mg/kg per min. If begun before surgery, dopexamine was continued during the operation. After surgery, increased DO2I was maintained in patients in the protocol group until the blood lactate concentration decreased to less than 1.5 mmol/L. Both groups had similar perioperative fluid management.

Main outcome measures

Mortality and morbidity were recorded for 28 days after surgery. The number and types of complications, including infections and multiple-system organ failure, were also recorded.

Main results

Patients in the protocol group had a lower mortality rate than did patients in the control group (P = 0.01) (Table). Morbidity was also lower for patients in the protocol group. The mean number of complications per patient was 0.68 for the protocol group compared with 1.35 for the control group ({ 95% CI for the 0.67 difference 0.60 to 0.74 events/patient}*, P = 0.008).

Conclusion

Mortality and morbidity were reduced in patients at high risk for both when perioperative oxygen delivery was deliberately increased.

Source of funding: Fisons PLC, United Kingdom.

For article reprint: Dr. O. Boyd, The General Intensive Care Unit, St. George's Hospital, Blackshaw Road, London, SW17 0QT England, UK. FAX 44-81-767-5216.

*Numbers calculated from data in article.


Table. Increased perioperative oxygen delivery vs standard perioperative care for high-risk surgery†

Outcome at 28 d Increased oxygen delivery Standard care RRR (95% CI) NNT (CI)
Death 6% 22% 75% (22 to 92) 7 (4 to 28)

†Abbreviations defined in in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

The fundamental physiologic event that results in organ failure and death in critically ill patients is tissue hypoxia. In these patients, the optimization of tissue oxygen delivery and consumption are essential in reducing morbidity and mortality. Shoemaker and colleagues (1) have examined this concept in high-risk surgical patients and have shown that by using adequate fluid support and inotropic and vasodilatory agents, the attainment of a cardiac index > 4.5 mL/min per m2, tissue DO2I > 550 mL/min per m2, and tissue oxygen consumption > 167 mL/min per m2 resulted in improved survival.

This well-designed study by Boyd and colleagues provides additional support for the critical role of enhancing tissue DO2I by achieving "supranormal" hemodynamic parameters using dopexamine. This novel synthetic catecholamine increases cardiac index and reduces afterload while maintaining renal and splanchnic perfusion. Thus, patients allocated to treatment with dopexamine had a marked decrease in morbidity and mortality caused by multiple-system organ failure.

The practical applications of these findings for the clinician have been under scrutiny after this publication. A recent meta-analysis (2) of several randomized clinical trials of adults in the intensive care unit evaluated interventions (fluids, inotropes, and vasoactive drugs) designed to achieve supraphysiologic values of cardiac indexes, DO2, or VO2; this meta-analysis did not show a statistically significant reduction in mortality in critically ill patients. However, the authors also concluded that there may be a benefit in patients in whom the therapy is initiated preoperatively.

Two separate studies (3, 4) investigating the clinical utility of pulmonary artery catheterization in patients undergoing surgical procedures have shown that high-risk patients who have cardiac or peripheral vascular surgery might benefit by the use of invasive monitoring. However, multicenter, randomized, controlled trials are needed to confirm this assertion. A recent meta-analysis (4) of 16 randomized controlled trials studied the benefits of pulmonary artery catheterization-guided therapeutic strategies in critically ill patients and showed a modest but not statistically significant risk reduction in mortality. Conversely, it seems that a greater reduction in mortality occurred in patients who had pulmonary artery catheterization at the time of surgery.

On the basis of these findings, and despite the methodologic limitations, the inferences that can be drawn from these trials preclude any evidence-based clinical recommendation in the use of pulmonary artery catheterization and interventions to achieve an increase in oxygen delivery in critically ill patients. However, it is important to note that the timing of the intervention to achieve a supranormal cardiac index, DO2, or VO2, as done by Boyd and colleagues, might improve the outcome of high-risk surgical patients. Further randomized multicenter trials need to be done to answer this important question.

Hector O. Ventura, MD
Mandeep R. Mehra, MDOchsner Medical InstitutionsNew Orleans, Louisiana, USA


References

1. 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;94:1176-86.

2. Heyland DK, Cook DJ, King D, Kernerman P, Brun-Buisson C. Maximizing oxygen delivery in critically ill patients: a methodologic appraisal of the evidence. Crit Care Med. 1996;24:517-24.

3. Leibowitz AB, Beilin Y. Pulmonary artery catheters and outcome in the perioperative period. New Horiz. 1997;5:214-21.

4. Ivanov RI, Allen J, Sandham JD, Calvin JE. Pulmonary artery catheterization: a narrative and systematic critique of randomized controlled trials and recommendations for the future. New Horiz. 1997;5:268-76.