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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low-dose norepinephrine infusion | Experimental | Participants receive a norepinephrine infusion at 0.05 micrograms/kg/min starting 3 minutes before fentanyl during standardized induction of general anesthesia. |
|
| 0.9% sodium chloride infusion | Placebo Comparator | Participants receive 0.9% sodium chloride with the same presentation, timing, and infusion settings as the intervention arm during standardized induction of general anesthesia. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Norepinephrine (0.05 μg/kg/min) | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative duration of MAP below 65 mmHg during induction | Total time with mean arterial pressure below 65 mmHg, derived from time-stamped arterial line data after removal of artifacts. | From start of propofol administration to 10 minutes after endotracheal intubation |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of MAP below 65 mmHg | Proportion of participants with at least one episode of MAP below 65 mmHg. | From start of propofol administration to 10 minutes after endotracheal intubation |
| Incidence of severe hypotension (MAP below 55 mmHg) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Thang Toan Nguyen, PhD | Contact | +084916874795 | nguyentoanthang@hmu.edu.vn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Anesthesia and Surgical Intensive Care, Bach Mai Hospital | Hanoi | Vietnam |
The investigators have not yet determined whether de-identified individual participant data will be shared. Any future data sharing decision will depend on institutional policy, ethics approval requirements, and participant privacy considerations.
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| ID | Term |
|---|---|
| D010538 | Peritonitis |
| ID | Term |
|---|---|
| D059413 | Intraabdominal Infections |
| D007239 | Infections |
| D010532 | Peritoneal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D009638 | Norepinephrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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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.
|
| Placebo | Other | 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. |
|
Proportion of participants with at least one episode of MAP below 55 mmHg.
| From start of propofol administration to 10 minutes after endotracheal intubation |
| Largest decrease in MAP from baseline | Maximum absolute and relative reduction in MAP compared with baseline. | From baseline before study-drug infusion to 10 minutes after endotracheal intubation |
| Number of Participants Requiring Rescue Vasopressor | Number of participants who receive any rescue vasopressor to treat hypotension during the induction-intubation study window. | From baseline before study-drug infusion to 10 minutes after endotracheal intubation |
| Number of Participants With Bradycardia | Number of participants with bradycardia during the induction-intubation study window. Bradycardia should be defined according to the protocol-specified threshold | From start of propofol administration to 10 minutes after endotracheal intubation |
| Postoperative lactate concentration | Arterial or venous lactate concentration used as an exploratory marker of tissue perfusion and physiologic recovery | Preoperative baseline and within 24 hours after surgery |
| Total Rescue Vasopressor Dose | Total dose of rescue vasopressor administered to treat hypotension during the induction-intubation study window. | From baseline before study-drug infusion to 10 minutes after endotracheal intubation |
| Number of Participants With Tachycardia | Number of participants with tachycardia during the induction-intubation study window. Tachycardia should be defined according to the protocol-specified threshold. | From start of propofol administration to 10 minutes after endotracheal intubation |
| Number of Participants Requiring Atropine | Number of participants who receive atropine according to the protocol-defined criteria during the induction-intubation study window. | From start of propofol administration to 10 minutes after endotracheal intubation |
| Number of Participants With Clinically Significant Arrhythmias | Number of participants with clinically significant arrhythmias during the induction-intubation study window. | From start of propofol administration to 10 minutes after endotracheal intubation |
| Number of Participants Admitted to the Intensive Care Unit After Surgery | Number of participants transferred to the intensive care unit (ICU) after surgery. | From end of surgery to hospital discharge |
| Number of Participants With Early Postoperative Complications | Number of participants with predefined early postoperative complications after surgery. | From end of surgery to hospital discharge |
| Postoperative Length of Stay | Postoperative length of hospital stay from the end of surgery until hospital discharge. | From end of surgery to hospital discharge |
| D000588 |
| Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |