The origin of DO2 and the magic 600….

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 Journal  1988; 94: 1176-1186.

RHH Journal Club. June 13th, 2013. Dr Andy Cruikshanks

Full-text article (if available)

Does the targeting of supranormal oxygen delivery reduce mortality in high-risk surgical patients?

Study Design

This paper was an amalgamation of two separate prospectively randomised trials (or series) carried out at a single centre in the USA between 1978-1980 and 1983-1984.

Methodology (Series 1)

252 high risk surgical patients were randomised to receive either standard resuscitation following normal goals (control) or resuscitation titrated to supranormal physiological end-points, most notably DO2 > 600 and CI >4.5. Patients were followed up and classified as either survivors, survivors-with-complications and non-survivors.

  • Population: 252 high risk surgical patients presenting to a single USA centre between 1978-1980 selected according to 11 loosely pre-defined criteria
  • Intervention: 101 patients received a mixture of pre and post-operative optimisation to achieve targets of DO2 > 600 and CI >4.5
  • Control: 151 patients received a mixture of pre and post-op resuscitation to achieve normal physiological goals.
  • Primary Outcome: In-hospital mortality

Validity (Series 1)

  • Randomisation based on a pre-specified on-call pattern of the surgical residents – ie. not random!
  • Not blinded.
  • No protocol or explanation of methods for achieving resuscitation targets.
  • Difficult to infer whether patients were analysed in their randomisation groups.

Results (Series 1)

  • Statistically significantly lower mortality in the supranormal group
  • Multiple non-pre-specified sub-group analyses also demonstrated improved mortality in the supranormal groups

Methodology (Series 2)

146 high risk surgical patients were pre-operatively randomised into three arms: a CVP control arm, a Pulmonary artery catheter (PAC) control and a PAC intervention arm. In the interventional arm the same supranormal physiological end-points, most notably DO2 > 600 and CI >4.5

  • Population: 146 patients presenting to the same US centre between 1983-1984 identified according to the same 11 pre-defined high risk criteria.
  • Intervention: 28 patients received pre and post-operative optimisation using PAC to achieve set physiological targets, including those of DO2 > 600 and CI >4.5.
  • Control 1: 30 patients received pre and post-operative optimisation using PAC to achieve set physiological targets, with normal values for DO2 and CI.
  • Control 2: 30 patients received pre and post-operative optimisation using CVP to achieve set physiological targets, without any DO2 or CI targets.
  • Primary Outcome: In-hospital mortality

Validity (Series 2)

  • Randomisation: Prospectively via a random number table
  • Not blinded
  • No protocol or explanation of methods for achieving resuscitation targets.
  • Patients were largely analysed in the groups into which they were randomised however 3 patients were not analysed which may be significant given the small numbers in this trial.

Results (Series 2)

  • Statistically significant difference in mortality between PAC intervention and PAC control arms
  • However no statistical difference in mortality between PAC intervention arm and CVP control arm.
  • Reduction in many post-op complications however these were not defined and were not pre-specified as secondary outcomes.

Application

  • This was a single centre study with methodological flaws that demonstrated a reduction in mortality when resuscitation was aimed at producing supranormal values for oxygen delivery and cardiac output.
  • Numerous attempts to repeat have produced few successes.
  • The techniques and end-points for resuscitation used have been largely superceded since.

Take home Message:

Whilst this trial has little applicability to current practice this paper is in part responsible for concepts such as goal-directed therapy and fluid resuscitation strategies in enhance recovery

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