Blood Pressure, Complication,Postoperative, Intraoperative Hypotension
Conditions
Keywords
Blood pressure, Intraoperative Hypotension, Postoperative complications, Postoperative mortality
Brief summary
This study is a multicenter randomized controlled trial comparing two strategies of mean arterial blood pressure management (MAP ≥ 80mmHg vs MAP ≥ 65 mmHg) in high-risk surgical patients undergoing elective laparotomic/laparoscopic surgery.
Detailed description
Intraoperative hypotension has been associated with major postoperative complications after non-cardiac surgery. However, is is still unclear the optimal intraoperative mean arterial pressure (MAP) target in the subgroup of those patient with an history of hypertension at home, and at risk of developing postoperative complications. The objective of this study is to assess the effects of an intraoperative blood pressure management strategy aiming at keeping the MAP ≥ 80mmHg), as compared to the conventional practice (to maintain intraoperative MAP ≥ 65mmHg), on a composite outcome considering the death rate and the incidence of major events in patient scheduled for elective laparotomic/laparoscopic surgery. The primary outcome is a composite of 30-days from operation mortality rate and at least one major organ dysfunction including the renal, respiratory, cardiovascular and neurologic systems or new onset of sepsis and septic shock occurring by day 7 after surgery.
Interventions
DRUGEphedrine
In both the group, the target MAP can be maintained by means of bolus of ephedrine (2.5 mg). The maximal dose for the ephedrine allowed is 25 mg (10 boluses of 2.5 mg), after this threshold a continuous infusion of norepinephrine will be started
DRUGNorepinephrine
In both the group, the target MAP can be maintained by means of bolus of ephedrine (2.5 mg) or Etilefrine (1 mg). The continuous infusion of norepinephrine, as decided by the attending anesthetist, may be started at any point of the intraoperative period. The starting dose of norepinephrine is the lowest needed to reach the predefined MAP target.
DRUGEtilefrine Hydrochloride bolus
The maximal dose for the etilefrine allowed is 10 mg (10 boluses of 1 mg), after this threshold a continuous infusion of norepinephrine will be started
DIAGNOSTIC_TESTUse of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)
PPV, SVV and mini\_FC will guide fluid bolus administration during an episode of intraoperative hypotension, following two predefined algorithms for laparotomic/non laparotomic surgery
Sponsors
Humanitas Clinical and Research Center
Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The trial intervention is not blinded for investigators, clinical staff, and patients, as blinding intraoperative MAP target is not feasible. The physicians of each center assessing all postoperative outcomes will be masked for the allocation.
Intervention model description
The study will be a multicentric, randomized, non-blinded clinical trial. Eligible patients will be assigned in a 1:1 ratio to either a to control or treatment group. Randomization list will be created by a computer with the use of a permuted block design and embedded in the Electronic Case Report Form. Randomization will be performed using a 'block of 6 and stratified according to predefined baseline characteristics: 1. Age ≥ 75 years 2. Preoperative systolic pressure 1. \< 140 mmHg 2. ≥ 140 mmHg
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(all the following) 1. Adult patients ≥ 60 years 2. History of chronic hypertension requiring home therapy. 3. Scheduled for major elective abdominal surgery (laparoscopic, robotic or laparotomic) 4. Expected surgical duration of at least 3 hours. 5. Needing invasive arterial and hemodynamic monitoring as decided by the attending anesthetist, according to the rules of good clinical practice of each involved center. AND At increased risk of postoperative complications (at least one of the following): 1. American Society of Anesthesiologists (ASA) class 3 or 4 2. Known or documented history of coronary artery disease (angina, myocardial infarction or acute coronary syndrome). 3. Known or documented history of peripheral vascular disease. 4. Known or documented history of heart failure requiring treatment. 5. Ejection fraction less than 30% (echocardiography) 6. Signs of diastolic moderate to severe dysfunction or chronic hypertensive cardiomyopathy (echocardiography) 7. Moderate or severe valvular heart disease (echocardiography) 8. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Radiographically confirmed or according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. 9. Diabetes currently treated with an oral hypoglycemic agent and/or insulin 10. Morbid obesity (BMI ≥35 kg/m2) 11. Preoperative serum albumin \<30 g/l 12. Anaerobic threshold (if done) \<14 ml/kg/min 13. Exercise tolerance equivalent to six metabolic equivalents (METs) or less as defined by American College of Cardiology/American Heart Association guidelines
Exclusion criteria
1. Refusal of consent 2. Chronic kidney disease with glomerular filtration rate \<30 ml/min/1.73 m2 or requiring renal-replacement therapy for end-stage renal disease 3. Acute cardiovascular event, including acute or decompensated heart failure and acute coronary syndrome (within prior 30 days). 4. Urgent or time-critical surgery 5. Aortic or Renal vascular surgery (including nephrectomy) 6. Liver Surgery 7. Neurosurgery 8. Surgery for palliative treatment only or ASA physical status 5 9. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite endpoint of postoperative mortality and at least one major organ dysfunction (see description in the secondary outcomes). | up to 30 days after operation | Composite postoperative outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU stay (days) | up to 30 days after operation | Intensive Care Unit stay (days) |
| ICU readmission | up to 30 days after operation | Intensive Care Unit readmissions |
| Sequential Organ Failure Assessment (SOFA) scores on postoperative | up to 7 days after operation | Postoperative organ failure - SOFA scores ranges from 0 (\<2% of mortality) to 24 (\>90% of mortality) |
| Overall intraoperative fluid balance | day 1 after the operation | Intraoperative infusions (crystalloids, colloids, blood products) / Intraoperative loss balance (urine output) |
| Mortality | up to 30 days after operation | Mortality |
| Vasopressors use | day 1 after the operation | Dose and timing of vasoactive drug infusion intraoperatively |
| Need for reoperation | day 30 after operation | Need of a new surgical treatment |
| Hospital stay (days) | up to 30 days after operation | Hospital stay (days) |
Other
| Measure | Time frame | Description |
|---|---|---|
| RESPIRATORY | day 7 after operation | * Acute respiratory distress * Hypoxemia with or without acute respiratory distress * Need for invasive, non-invasive ventilation or high-flow nasal cannula for acute respiratory distress. * Acute respiratory distress syndrome. * Pulmonary edema * Pulmonary embolism |
| RENAL | day 7 after operation | • Acute Kidney Injury (AKI) and AKI stages defined according to the AKIN classification/staging system of acute kidney injury |
| SEPSIS and Septic shock | day 7 after operation | Based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria, sepsis required a quick Sequential Organ Failure Assessment (qSOFA) Score ≥ 2 points due to infection, septic shock defined as indicated by the Surviving Sepsis Campaign Guidelines |
| CARDIOVASCULAR complications | day 7 after operation | * Acute heart failure * Myocardial injury after non-cardiac surgery * Myocardial infarction * Bradycardia * Symptomatic proximal deep venous thrombosis * Peripheral arterial and venous thrombosis |
| NEUROLOGICAL complications | day 7 after operation | * Stroke * Subarachnoid hemorrhage * Cerebral venous thrombosis * Seizure * Acute delirium |
Countries
Italy
Outcome results
None listed