Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery A Randomized Clinical Trial. 

The Journal of the American Medical Association. 2017;318(14):1346–1357 doi:10.1001/jama.2017.14172

Presented by: Dr J Lloyd


Perioperative hypotension is known to be related to post operative organ dysfunction, in particular the heart, lungs, and kidneys.

Patients at high-risk of post operative organ dysfunction are also at an increased risk of mortality.

Hypertension is an increasingly common comorbidity, especially in the elderly population, and it alters the autoregulatory capacity of their brain and kidneys leaving them more vulnerable to ischaemia during an episode of hypotension than organs of normotensive patients. It is thus hypothesised that maintaining a higher systolic blood pressure during surgery, in high risk patients with hypertension, will reduce the risk of post operative organ dysfunction.

Guidelines for critical care have suggested altering haemodynamic targets to premorbid levels in hypertensive patients, but there is no good evidence for the same advice in the operating theatre.

This study aims to determine whether adjusted intraoperative haemodynamic targets in hypertensive patients can reduce the incidence of post operative organ dysfunction, and mortality

Design & Setting

A multi-centre, stratified, parallel control group randomised clinical trial conducted across 9 hospitals in France


Patients over 50, with an ASA classification of II or greater, undergoing surgery with an expected duration of over 2 hours, and with an acute kidney injury risk index of III or higher (see figure below)

JC 6th Feb figure

Figure from: KheterpalS,TremperKK,HeungM,etal. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009;110(3):505-515.


The patients reference blood pressure was measured preoperatively, and then the two arms of the study were protocolled as follows:

  • Experimental group – a 2.5mg in 250ml noradrenaline infusion was administered peripherally to maintain a systolic blood pressure within 10% of the reference pressure.
  • Control group – 6mg boluses of ephedrine (up to a maximum of 60mg before the use of rescue noradrenaline was permitted) were used to treat any drops in systolic BP below 80mmHg or any more than 40% below the reference pressure.

Other aspects of care were standardised such as:

  • Measurement of BP through a radial arterial line
  • Anaesthetic induction with the use of propofol 2-3 mg/kg, sufentanil 0.2 μg/kg and cis-atracurium 0.15 mg/kg. Inhaled anesthetics used for maintenance of general anesthesia, to a target bispectral index between 40 and 60, in addition to intravenous perfusion of sufentanil at 0.1 to 0.2 μg/kg per hour.
  • Mechanical ventilation with the use of a tidal volume between 8 and 10 ml/kg predicted body weight, with a positive end-expiratory pressure between 5 and 10 cmH2O, an inspired oxygen fraction (FIO2) to maintain oxygen saturation ≥95% and the respiratory rate adjusted to maintain end-tidal carbon dioxide concentration between 30-35 mmHg.
  • Blood transfusion to maintain hemoglobin level at greater than 10 g/dl.
  • Core temperature maintained at 37°C.


Primary outcome is a composite measure that includes both meeting the SIRS criteria, as well as demonstrating major organ dysfunction from either the cardiovascular, respiratory, renal, neurological, or coagulation systems within 7 days of the operation.

Secondary outcomes included

  • Intraoperative blood pressure variability, blood loss volume, transfusion requirement, fluid requirements, and rescue vasopressor therapy, as well as incidence of either hypotension, hypertension, or bradycardia
  • Post operative urine output, RIFLE score, requirement for renal replacement, SOFA score, duration of ICU and hospital stay, as well as a wide range of specified postoperative complications within 30 days


The primary outcome event incidence was 38.1% in the treatment group and 51.7% in the control group, this gave an adjusted relative risk of 0.73 with 95% CI of 0.56 to 0.94; P = .02

Of the secondary outcomes:

  • Renal dysfunction occurred in 32.7% in the treatment group Vs 49% in the control group (adjusted relative risk 0.70 with 95% CI of 0.53 to 0.92; P = .01)
  • Altered neurological function occurred in 5.4% of the treatment group Vs 15.9% of the control group (adjusted relative risk, 0.34; 95% CI, 0.16 to 0.75; P = .007)


Individualised targeting of systolic blood pressure in high risk patients reduces the risk of both post operative renal and neurological dysfunction


  • Adequately powered, well designed randomised control study, with clear inter group standardisation of care
  • A clinically relevant question


  • The two regimes use two different vasopressors to attain their haemodynamic goals, so it is possible that some of the difference in outcomes could be from a pharmacological rather than haemodynamic difference.
  • Reference values for preoperative blood pressure values may not always be available in clinical practice for example with emergency surgery.
  • Necessary lack of intervention blinding for the anaesthetists delivering care
  • HES boluses to achieve maximal cardiac index is no longer standard practice, although it was the same protocol in both groups
  • Large numbers of patients were excluded based on their risk score for post operative renal impairment, which means we cannot extrapolate the results to answer the question about how this majority of patients should be treated


  • In cases of expected prolonged surgery, where patients are known to be at risk of post operative renal dysfunction, maintaining systolic pressures of within 10% of their baseline will decrease the risk of post operative renal and neurological dysfunction.
  • It also demonstrates the safety of peripheral dilute noradrenaline, as no adverse outcomes were reported

Potential for impact

Widespread application of the conclusions has the potential to reduce morbidity in a high risk patient group