Effect of Individualised vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial Futier E, Lefrant J-Y, Guinot P-G et al. JAMA. 2017;318(14):1346-1357
“One man’s ceiling is another man’s floor” – Paul Simon
Summary by Dr Stephen Howey
Haemodynamic instability is common intraoperatively and hypotension is a preventable risk factor for renal, cardiac and neurological morbidity. The appropriate use of IV fluids and/or vasopressors can offset this risk, however the optimal BP target lacks common consensus (previous literature has variously advocated systolic arterial pressure <80mmHg, mean <60mmHg, or within 20-40% of patients baseline BP as targets to treat).
Does a strategy based on individualised blood pressure reduce post-operative complications among patients undergoing major abdominal surgery?
- Nine French university and non-university Hospital sites
- Stratified, parallel-group RCT with intention-to-treat analysis.
- Patients randomly assigned 1:1 ratio to either study arm via web-based minimisation algorithm.
- Patients, statisticians and data collectors all blinded.
Primary Outcome: Composite of systemic inflammatory response syndrome (SIRS) and at least 1 organ system dysfunction (renal, cardiac, pulmonary, neurological, coagulation – all clearly defined)
Secondary Outcomes: incidences of intraop hypotension, hypertension, bradycardia, incidence of sepsis, total fluid volume, 30-day postop complications, length of stay in ICU and hospital, all-cause mortality.
Inclusion criteria: ≥50 years, major abdominal or non-abdominal surgery with expected surgical duration of at least 2 hours, ASA ≥II, Acute Kidney Injury (AKI) risk index ≥III
Exclusion criteria: Severe untreated/uncontrolled hypertension despite medications (≥180/110), end-stage renal disease, preoperative sepsis, circulatory shock or acute cardiac decompensation, preoperative norepinephrine infusion before study entry, surgical procedure under regional anaesthesia (both epidural and spinal anaesthesia), pregnancy/breast feeding, patient refusal or concomitant trial
All patients received a standardised GA (Induction: propofol 2-3 mg/kg, sufentanil 0.2 μg/kg and cisatracurium 0.15 mg/kg). Maintenance inhaled anaesthetics targeted a bispectral index between 40 and 60, with an IV sufentanil infusion at 0.1-0.2 μg/kg/hr. Fluids followed a goal-directed therapy approach with 250ml aliquots of colloid (HES 6%) to maintain SVI ≤10%, plus a maintenance of 4ml/kg/hr Ringer’s Lactate solution. Patients were mechanically ventilated, temperature controlled and Hb kept ≥100g/l. Epidural analgesia was authorised for use postoperatively only, and use of ketamine, benzodiazepines and NSAIDs was prohibited.
Control group: patients received 6mg IV boluses of ephedrine (max 60mg) to treat any drop in SBP below 80 mmHg, or lower than 40% from the patient’s resting BP (preop BP in clinic used as the reference value) – with norepinephrine as a rescue strategy.
Intervention group: individualised (preventive) treatment strategy, where patients received continuous peripheral infusion of norepinephrine (10mcg/ml) to maintain SBP within ±10% of the reference BP, initiated at a dose according to the patient’s weight.
Observations were recorded every 10 minutes and for 4 hours post-operatively, with a radial arterial catheter.
Altogether, 1494 patients were eligible but 80% were excluded for not meeting inclusion criteria (of which 75% were due to an AKI risk score under 3).
There were 298 patients randomised; n=147 intervention vs standard n=145 after dropouts.
- Baseline characteristics similar, 49% over 70yo, with reference BP almost identical. 84% of procedures were elective and the vast majority (>94%) was abdominal surgery. Significant proportion of patients in both groups had pre-existing chronic arterial hypertension (n=240, 82%)
- More patients in the control group had existing heart failure or IHD
Individualised BP strategy meant the mean study systolic BP was 123mmHg vs 116 (control group)
This resulted in a lower primary composite outcome event rate in intervention group:
- 38.1% in intervention group compared to 51.7% in control; absolute risk reduction (ARR): 14% (95% CI -25% to -2%; p = 0.02), number needed to treat (NNT): 8
- Renal dysfunction lower in intervention group 32.7% vs control 49.0%; ARR: 16% (95% CI -27% to -5%; p = 0.01), NNT: 7
- Altered consciousness lower in intervention group 5.4% vs control 15.9%; ARR: 10% (95% CI -17% to -3%; p = 0.007), NNT: 10
- No significant difference in: SIRS score, coagulation SOFA score, hypoxaemia, pneumonia, ARDS, reintubation rates, SOFA scores on day 1, 2 and 7, incidence of sepsis, surgical complications, all cause mortality at 30 days
Targeting an intraoperative BP closer to the patients resting BP significantly reduces the incidence of postop organ dysfunction in high risk patients undergoing major non-cardiac surgery
Strengths: Randomised-control trial, pertinent topic, mostly well-matched groups, high-risk patient population, pre-registered on clinicaltrials.gov, no conflicts of interest
- study did not just compare the BP strategies as it outlined; it was also norepinephrine vs ephedrine, and IV infusion vs boluses, thus confounding the results.
- Evidence behind some of practices controversial and not directly translatable to current practice including use of HES starch / link to renal injury, maintaining Hb>100g/l, goal directed fluid therapy
- The high incidence of primary events was heavily skewed by renal morbidity (any stage on RIFLE scoring system), which was to be expected, given patients were only included if they were sufficiently at risk of AKI
- No reporting of complications from mandatory arterial line insertion or how much opiate used postop
- No record of duration of hypotensive events, especially with observations every 10 minutes
Overall thoughts. This is further evidence to support a higher incidence of perioperative complications in patients subjected to intraoperative hypotension, though this study alone is unlikely to be the definitive voice in this area.