Renin Angiotensin System, Surgery
Conditions
Keywords
Major surgery, Postoperative morbidity and mortality, Renin angiotensin system inhibitors
Brief summary
More than 200 million major surgical procedures are performed annually worldwide. Many of these patients have comorbidities including hypertension and/or heart failure. Chronic treatment of hypertension and/or heart failure very often includes a Renin-Angiotensin System (RAS) inhibitor (Angiotensin-Converting Enzyme Inhibitors (ACE-Is) or Angiotensin Receptor Blockers (ARBs). To stop or not to stop these medications before major surgery remain unknown. Data on management of RAS inhibitors before major surgery and anesthesia remain lacking and matter of debate. It is much likely that the strategy regarding management of RAS inhibitors in the peri-operative setting have important impact on peri-operative complications. The lack of evidence leads to conflicting guidelines with respect to RAS inhibitors management before major surgery. While French guidelines are to stop RAS inhibitors patients with hypertension to avoid profound anesthestic-drugs-induced hypotension, international guidelines differ. The American heart association task force states that continuation of RAS inhibitors perioperatively is reasonable (class IIa recommendation,level of evidence: B). The purpose of this study is to determine the prognostic impact of withholding vs continuing ARBs before major non cardiac surgery.
Detailed description
Multicenter, prospective, randomized, pragmatic, parallel-group clinical trial. The inclusion visit takes place between 4 months and no later than 3 days before the surgery visit. * The randomization will be performed by the anesthesiologist Control group : RAS-I discontinuation Experimental group: RAS-I continuation * A prescription for the medication strategy (stopping or pursuing the medication) will be handed to the patient during the anesthesiology consultation. Five follow-up visits are planned * Immediately, one hour after the surgery (Day 0) * Then four follow-up visits are planned on day 1, 2, 7 (or hospital discharge) and 28 days+15 days (43 days maximum) after surgery will be collected data and parameters for study endpoints. End of research visit is the 28 days+15 days (43 days maximum) follow-up visit.
Interventions
PROCEDUREcontinuation of the RAS-inhibitors
drug intake
PROCEDUREdiscontinuation of the RAS-inhibitors
no drug intake
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Masking description
Endpoint validated by an adjudication commitee blinded to the arm.
Intervention model description
The aim of this study is to evaluate the impact of Renin-Angiotensin System inhibitors management (Continuation or discontinuation 48 hours before surgery) on outcome in patients undergoing scheduled major non-cardiac surgery (surgery with an expected duration of more than 2 hours from the surgical incision and a post-operative hospital stay of least 3 days)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patients requiring major non-cardiac surgery (surgery with an expected duration of more than 2 hours from the surgical incision and a post-operative hospital stay of least 3 days) (according to the study RELIEF, DOI : 10.1056/NEJMoa1801601)) * Age≥18 years * Patients chronically treated (\>3 months before surgery) with RAS inhibitors * Pregnancy test at inclusion visit for women of childbearing potential Women of childbearing potential must agree to use adequate contraception according to Recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG) * Signed informed consent
Exclusion criteria
* Emergency surgery (surgical treatment needed within 24 hours) * Hyperkalemia (\> 5.5mmol/L) known at the time of the anesthetic consultation * Patients for which death is deemed imminent and inevitable or patients with an underlying disease process with a life expectancy of less than 1 month * Patient with severe renal insufficiency, known at the time of the anesthestic consultation (as defined by estimated glomerular filtration rate (creatinine clearance \<15 ml/min/1.73m2 or requiring renal replacement therapy) * Patient with preoperative shock (defined by the need for vasoactive drugs before surgery) * Inability to obtain informed consent either from the patient. * Lack of Social Insurance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| composite outcome composed of all-cause mortality and major postoperative complications within 28 days after surgery. | after surgery until day 28 | Complications will be validated by an adjudication committee, blinded to the treatment arm. Death; Acute Myocardial infarction; Arterial or venous thrombosis; Stroke; Acute pulmonary oedema; Post-operative cardiogenic shock; Acute severe hypertension crisis; Cardiac arrhythmia requiring therapeutic intervention; Postoperative episodes of sepsis; Postoperative respiratory complication; Need for unplanned intensive care unit admission or readmission; Acute kidney injury: KDIGO criteria Baseline serum creatinine is obtained from the pre-operative blood sample; Surgical complications: need for reoperation for any reason and radiologic interventions for abscess drainage; Severe Hyperkalemia: serum potassium level \>5.5 mmol/L and requiring therapeutic intervention (insulin/glucose infusion and/or sodium bicarbonate infusion and/or intravenous B2 agonists and/or intravenous calcium gluconate and/or renal replacement therapy and/or ventricular tachycardia or ventricular fibrillation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Episodes of hypotension | during anesthesia and surgery | Episodes requiring vasopressors administration |
| Acute kidney injury | after surgery until day 28 | according to the KDIGO criteria |
| Maximum SOFA score | from postoperative day 1 to day 7 | patients admitted to ICU |
| Duration of hospital stay | after surgery until day 28 | Patients who will be outside the hospital but in other types of health care facilities at day 28 will be considered to have been discharged home |
| Hospital free-days | censored at 28 days following surgery | Duration after hospital discharge |
Countries
France
Outcome results
None listed