HIgh Versus STAndard Blood Pressure Target in Hypertensive High-risk Patients Undergoing Major Abdominal Surgery

NCT ID: NCT05637606

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 636 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-06
• Study Completion Date: 2025-05-21

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.

Conditions

Blood Pressure; Complication,Postoperative; Intraoperative Hypotension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

MAP 80

Intervention group: intraoperative mean blood pressure target \> 80 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 80 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.

Group Type: EXPERIMENTAL

Ephedrine

Intervention Type: DRUG

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

Norepinephrine

Intervention Type: DRUG

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.

Etilefrine Hydrochloride bolus

Intervention Type: DRUG

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

Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)

Intervention Type: DIAGNOSTIC_TEST

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

MAP 65

Control group: intraoperative mean blood pressure target \> 65 mmHg. Treatment of hypotension (defined as a mean blood pressure of below 65 mmHg) using intravenous bolus or continuous infusion of vasopressors, or fluids using a dedicated algorithm considering the pulse pressure or stroke volume variation and the mini fluid challenge to optimize mean blood pressure values.

Group Type: OTHER

Ephedrine

Intervention Type: DRUG

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

Norepinephrine

Intervention Type: DRUG

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.

Etilefrine Hydrochloride bolus

Intervention Type: DRUG

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

Use of pulse pressure and stroke volume variation (PPV and SVV); use of Mini Fluid Challenge (mini_FC)

Intervention Type: DIAGNOSTIC_TEST

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

Interventions

Ephedrine

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

Intervention Type: DRUG

Norepinephrine

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.

Intervention Type: DRUG

Etilefrine 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

Intervention Type: DRUG

Use 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

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Ephedrine bolus; norepinephrine infusion; Hemodynamic optimization

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva

OTHER

Sponsor Role: collaborator

Humanitas Clinical and Research Center

OTHER

Sponsor Role: lead

Responsible Party

Antonio Messina

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Antonio Messina

Role: PRINCIPAL_INVESTIGATOR

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy

Locations

Ospedali Riuniti Foggia- Università di Foggia

Foggia, Apulia, Italy

Department of Anesthesia and Intensive Care, University Hospital of Modena

Modena, Emilia-Romagna, Italy

Policlinico A. Gemelli

Rome, Lazio, Italy

Humanitas Research Hospital

Rozzano, MILANO, Italy

Fondazione Istituto San Raffaele G. Giglio

Cefalù, Sicily, Italy

Careggi University Hospital

Florence, Tuscany, Italy

Unit of Anesthesiology and Intensive Care B, Department of Surgery, Dentistry, Gynecology and Pediatrics, AOUI-University Hospital Integrated Trust of Verona

Verona, Veneto, Italy

Azienda Ospedaliero - Universitaria SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Istituto Nazionale dei Tumori

Milan, , Italy

Ospedale Antonio Cardarelli

Napoli, , Italy

Azienda sanitaria Friuli Occidentale (AsFO]

Pordenone, , Italy

Ospedale Santo Stefano

Prato, , Italy

Ospedale S. Anna di Castelnovo ne' Monti

Reggio Emilia, , Italy

Sant'Eugenio ASL Roma 2:

Roma, , Italy

Azienda Ospedaliero Universitaria di Sassari

Sassari, , Italy

Ospedale Molinette

Torino, , Italy

Ospedale Santa Chiara di Trento

Trento, , Italy

Countries

Italy

References

Messina A, Robba C, Calabro L, Zambelli D, Iannuzzi F, Molinari E, Scarano S, Battaglini D, Baggiani M, De Mattei G, Saderi L, Sotgiu G, Pelosi P, Cecconi M. Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery. Crit Care. 2021 Feb 1;25(1):43. doi: 10.1186/s13054-021-03464-1.

Reference Type: BACKGROUND

PMID: 33522953 (View on PubMed)

Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26.

Reference Type: BACKGROUND

PMID: 23835589 (View on PubMed)

Other Identifiers

HISTAP TRIAL

Identifier Type: -

Identifier Source: org_study_id