Effect of Individualised vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery

The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study

Futier E, Lefrant Y, Pierre-Gregoire Guinot et al.

JAMA 2017; 318 (14): 1346-57. doi:10.1001/jama.2017.14172


In high risk patients undergoing abdominal surgery, does treating patients with an individualised systolic blood pressure target reduce the risk of post-operative organ dysfunction when compared to standard practice?

Study Design

Multi-centre, randomised, parallel-group clinical trial

From December 4, 2012 – August 28, 2016

Across 9 French university and non-university hospitals

Adult patients (1494 screened, 1194 excluded, n = 298) at increased risk of postoperative complications

Randomised and stratified, 1:1 ratio of control to intervention groups

90% power, 2-sided a-level of 0.05, intention to treat analysis

Inclusion criteria:

  • Age ≥50
  • Scheduled to undergo surgery under general anaesthesia
  • Expected duration ≥2 hours
  • ASA class ≥II
  • Preoperative acute kidney injury risk index class ≥III

Exclusion criteria

  • Severe uncontrolled hypertension (SBP ≥180 mmHg or DBP ≥110 mm Hg)
  • Chronic kidney disease stage ≥ IV
  • Acute or decompensated heart failure or ACS
  • Pre-operative sepsis or circulatory shock
  • Already on noradrenaline
  • Surgery under regional/intra-thecal anaesthesia
  • Required renal vascular surgery
  • Pregnant or breast feeding
  • Enrolled in another study
  • Patient refusal
  • Not enrolled in French  healthcare


Intervention period from induction to 4h post-surgery

IBP monitoring intra and post-op via radial arterial line

Intervention group received a noradrenaline infusion upon induction and titrated to target SBP within 10% of reference BP

Control group were given ephedrine boluses (6mg up to 60mg) treating SBP <80 mmHg or >40% from the reference value during and for 4 hours following surgery

Both groups received fluids, CSL 4 ml/kg per hour as intra-op maintenance alongside boluses of 250ml colloid (hydroxyethyl starch 130/0.4/6%) given to optimise SVI

Haemoglobin was maintained with transfusions to a target of >100g/L

Post-operative care was at the discretion of the local team


Primary outcome composite of SIRS + dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery

  • Renal – RIFLE stage of risk or higher
  • Respiratory – need for invasive or noninvasive ventilation
  • Cardiovascular – acute cardiac failure or myocardial ischaemia or infarction
  • Neurological – stroke or Glasgow Coma Scale score ≤14
  • Coagulation – SOFA subscore ≥2 points in the coagulation component

Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery.


292 completed trial

Primary outcome – Lower event rate in intervention group

  • 56/147 (38.1%) intervention group vs 75/145 (51.7%) control
  • Absolute risk reduction (ARR): 14% (95% CI -25% to -2%; P = 0.02)
  • Number needed to treat (NNT): 8
  • Fragility index 3

Postoperative organ dysfunction by day 30

  • 68/147 (46.3%) intervention group vs 92/145 (63.4%) in the standard treatment group
  • Adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84; P = .001)

Secondary outcomes

  • Renal dysfunction lower
    • 7% vs control 49.0%
    • ARR: 16% (95% CI -27% to -5%; P = 0.01), NNT: 7, FI: 7
  • Altered consciousness lower
    • 4% vs Control 15.9%
    • ARR: 10% (95% CI -17% to -3%; P = 0.007), NNT: 10, FI: 5
  • No significant difference in:
    • SIRS score
    • Coagulation SOFA score
    • Hypoxaemia
    • Pneumonia
    • ARDS
    • Re-intubation rates
    • SOFA scores on day 1, 2 and 7
    • Incidence of sepsis
    • Surgical complications
    • Severe adverse events or death at 30 days

Conclusions From Study

In high risk patients undergoing intra-abdominal surgery maintaining an individualised systolic blood pressure within 10% of resting/reference SBP with a noradrenaline infusion, reduced the risk of postoperative organ dysfunction (especially renal) compared with standard management of maintaining SBP>80mmHg or within 40% of reference SBP with ephedrine boluses.


  • Relevant question
  • No current accepted standard of treatment for SBP
  • Similar treatment and control groups
  • Significant difference in end intervention blood pressure (no difference pre-induction)
  • Outcomes clinically relevant
  • Bias minimised via randomisation online and post-op carers blinded


  • Primary outcome a composite score
  • Slow recruitment despite high number
  • Unblinded study
  • Large number of patients excluded with AKI risk index ❤ so may not be generalisable practice to lower risk populations
  • Unclear what the best value is to use for reference SBP – norm is often pre-induction
  • Use of invasive blood pressure needed
  • Noradrenaline given peripherally against local recommendations
  • Ephedrine only given in control group vs normal practice of ephedrine/metaraminol / phenylephrine
  • Duration of intra-operative hypotension not recorded
  • Threshold for treatment in the control group was lower than local practice

Summary by Dr A Feben. Journal Club Meeting 17 January 2019.

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