Post-induction Hypotension, Secondary Peritonitis
Conditions
Keywords
Emergency surgery, General anesthesia, Norepinephrine, Noradrenaline, Induction hypotension, Mean arterial pressure
Brief summary
This study tests whether giving a low-dose norepinephrine infusion just before induction of anesthesia can reduce low blood pressure during emergency surgery for peritonitis. Adults with secondary peritonitis who are scheduled for emergency surgery and have stable blood pressure after initial resuscitation will be randomly assigned to receive either norepinephrine or placebo (normal saline) during induction of anesthesia. The main outcome is the cumulative time spent with mean arterial pressure (MAP) below 65 mmHg from the start of propofol administration to 10 minutes after endotracheal intubation. The study will also evaluate rescue vasopressor use, heart rate changes, drug-related adverse events, and selected early postoperative outcomes.
Detailed description
The study is a single-center, randomized, double-blind, placebo-controlled interventional trial conducted at the Center for Anesthesia and Surgical Intensive Care, Bach Mai Hospital, Hanoi, Vietnam. Adults undergoing emergency surgery for secondary peritonitis often have marked hemodynamic vulnerability during induction of general anesthesia because of systemic inflammation, vasodilation, capillary leak, and relative hypovolemia. Propofol-based induction may further reduce arterial pressure and organ perfusion in this setting. Participants who meet eligibility criteria and have a mean arterial pressure (MAP) of at least 65 mmHg after initial resuscitation, without ongoing vasopressor support, will be enrolled and randomized 1:1 to a norepinephrine infusion group or a placebo group. In the intervention group, norepinephrine will be infused at 0.05 micrograms/kg/min starting 3 minutes before fentanyl. In the placebo group, 0.9% sodium chloride will be infused with the same presentation, timing, and pump settings. All participants will undergo a standardized induction protocol with fentanyl, titrated propofol, rocuronium, arterial line monitoring before induction, and protocolized hemodynamic rescue treatment. The primary endpoint is the cumulative duration of MAP below 65 mmHg during the induction-intubation window, defined from the start of propofol administration to 10 minutes after endotracheal intubation. Secondary endpoints include the incidence of MAP below 65 and below 55 mmHg, the largest decrease in MAP from baseline, heart-rate changes, rescue vasopressor requirements, atropine use, and predefined early postoperative outcomes.
Interventions
Norepinephrine prepared in a blinded syringe and infused continuously at 0.05 micrograms/kg/min starting 3 minutes before fentanyl during induction of general anesthesia. Infusion is adjusted or temporarily stopped according to the protocol-defined hemodynamic safety algorithm.
OTHERPlacebo
Placebo: 0.9% Sodium Chloride prepared in a blinded syringe and administered with the same timing, presentation, and pump settings as the active study drug.
Sponsors
Bach Mai Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Study drug syringes will be prepared by personnel not involved in anesthesia management, postoperative assessment, or statistical analysis. Participants, anesthesia care providers, investigators, outcome assessors, and statisticians will remain blinded to treatment allocation until database lock unless unblinding is required for participant safety.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged 18 years or older. * Secondary peritonitis requiring emergency surgery under general anesthesia with endotracheal intubation. * Planned induction with fentanyl, propofol, and rocuronium according to the study protocol. * Hemodynamically stabilized after initial resuscitation, with MAP at least 65 mmHg and no ongoing vasopressor infusion before induction. * ASA physical status I to III. * Written informed consent from the participant or a legally authorized representative.
Exclusion criteria
* Allergy or contraindication to norepinephrine, propofol, fentanyl, or rocuronium. * Severe cardiovascular disease likely to confound hemodynamic assessment, including decompensated heart failure, acute coronary syndrome, severe arrhythmia, severe valvular disease, or major cardiomyopathy. * Ongoing vasopressor therapy before induction. * Shock before surgery, including hypovolemic, septic, or cardiogenic shock. * Severe hypertension before induction (systolic blood pressure \>180 mmHg or mean arterial pressure \>110 mmHg). * Severe peripheral vascular disease or clinically significant limb ischemia. * Current monoamine oxidase inhibitor use. * Pregnancy or breastfeeding. * Contraindication to arterial catheter placement. * Refusal of consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative duration of MAP below 65 mmHg during induction | From start of propofol administration to 10 minutes after endotracheal intubation | Total time with mean arterial pressure below 65 mmHg, derived from time-stamped arterial line data after removal of artifacts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of MAP below 65 mmHg | From start of propofol administration to 10 minutes after endotracheal intubation | Proportion of participants with at least one episode of MAP below 65 mmHg. |
| Incidence of severe hypotension (MAP below 55 mmHg) | From start of propofol administration to 10 minutes after endotracheal intubation | Proportion of participants with at least one episode of MAP below 55 mmHg. |
| Largest decrease in MAP from baseline | From baseline before study-drug infusion to 10 minutes after endotracheal intubation | Maximum absolute and relative reduction in MAP compared with baseline. |
| Number of Participants Requiring Rescue Vasopressor | From baseline before study-drug infusion to 10 minutes after endotracheal intubation | Number of participants who receive any rescue vasopressor to treat hypotension during the induction-intubation study window. |
| Number of Participants With Bradycardia | From start of propofol administration to 10 minutes after endotracheal intubation | Number of participants with bradycardia during the induction-intubation study window. Bradycardia should be defined according to the protocol-specified threshold |
| Postoperative lactate concentration | Preoperative baseline and within 24 hours after surgery | Arterial or venous lactate concentration used as an exploratory marker of tissue perfusion and physiologic recovery |
| Total Rescue Vasopressor Dose | From baseline before study-drug infusion to 10 minutes after endotracheal intubation | Total dose of rescue vasopressor administered to treat hypotension during the induction-intubation study window. |
| Number of Participants With Tachycardia | From start of propofol administration to 10 minutes after endotracheal intubation | Number of participants with tachycardia during the induction-intubation study window. Tachycardia should be defined according to the protocol-specified threshold. |
| Number of Participants Requiring Atropine | From start of propofol administration to 10 minutes after endotracheal intubation | Number of participants who receive atropine according to the protocol-defined criteria during the induction-intubation study window. |
| Number of Participants With Clinically Significant Arrhythmias | From start of propofol administration to 10 minutes after endotracheal intubation | Number of participants with clinically significant arrhythmias during the induction-intubation study window. |
| Number of Participants Admitted to the Intensive Care Unit After Surgery | From end of surgery to hospital discharge | Number of participants transferred to the intensive care unit (ICU) after surgery. |
| Number of Participants With Early Postoperative Complications | From end of surgery to hospital discharge | Number of participants with predefined early postoperative complications after surgery. |
| Postoperative Length of Stay | From end of surgery to hospital discharge | Postoperative length of hospital stay from the end of surgery until hospital discharge. |
Countries
Vietnam
Contacts
CONTACTThang Toan Nguyen, PhD
Outcome results
None listed