Delayed Fluids in Hemorrhagic Shock Due to Severe Injuries. (PERMIT-LATAM)

Hospital Departamental de Villavicencio

Status: Begins enrollment in 2 months

Conditions: Intravenous Fluid Therapy; Trauma and Emergency Care; Shock,Hemorrhagic

Treatments: Drug: Crystalloid below 1000 mL.; Drug: IV fluids more than 1,000 mL

Study type: Observational

Funder types: Other

Identifiers

NCT07530653

GRIVI_2026_01_TMA_RESUSC

Details and patient eligibility

About

This study will provide information on the quality of care in hemorrhagic shock of severe injuries in a limited resource facility of Latin America, the strategies of fluid resuscitation, and outcomes.

Full description

Background / Introduction

Trauma remains a leading cause of mortality worldwide, particularly among young and economically productive populations, generating a disproportionate burden in terms of years of life lost, disability, and healthcare expenditures. Hemorrhagic shock is the most common cause of preventable death following trauma, especially within the first hours after injury. Despite advances in trauma systems and critical care, early mortality due to uncontrolled bleeding continues to pose a major clinical challenge.

Traditional resuscitation strategies have emphasized aggressive early fluid administration aimed at restoring normotension. However, growing evidence suggests that this approach may be physiologically detrimental in the setting of uncontrolled hemorrhage. Rapid volume expansion can dislodge forming clots, dilute coagulation factors, exacerbate acidosis, and contribute to the development of trauma-induced coagulopathy. These mechanisms are closely associated with the so-called "lethal triad" of trauma: hypothermia, acidosis, and coagulopathy, which significantly increases mortality risk.

In response to these concerns, the concept of delayed resuscitation, also referred to as permissive hypotension, has emerged as a damage control strategy. This approach aims to limit fluid administration until hemorrhage control is achieved, maintaining a lower-than-normal blood pressure sufficient for minimal organ perfusion while avoiding exacerbation of bleeding. Experimental models and clinical studies have suggested potential benefits, including reduced blood loss, lower transfusion requirements, and improved survival in selected patient populations.

However, the current body of evidence presents important limitations. Many studies have been conducted in high-resource settings with well-developed trauma systems, rapid surgical access, and availability of blood products. Furthermore, heterogeneity in study design, patient populations, injury patterns, and resuscitation protocols limits the generalizability of findings. Importantly, patients with traumatic brain injury, elderly individuals, and those with significant comorbidities may respond differently to hypotensive strategies, raising concerns regarding safety and applicability.

These uncertainties are particularly relevant in low- and middle-income countries (LMICs), including those in Latin America, where the burden of trauma is disproportionately high and healthcare systems often face resource constraints. In such settings, delays in definitive hemorrhage control, limited access to blood products, variability in prehospital care, and constrained intensive care capacity may influence both the feasibility and effectiveness of resuscitation strategies. Consequently, there is a critical need for context-specific evidence to guide clinical decision-making and optimize trauma care protocols in these environments.

Objective

To compare clinical outcomes in patients with hemorrhagic shock due to severe trauma according to the initial fluid resuscitation strategy, specifically delayed (permissive hypotension) versus immediate (conventional) resuscitation, in low-resource healthcare settings in Latin America.

Methods Study Design

This study is designed as a prospective, observational, analytical cohort study conducted in one or more tertiary-level trauma centers in Latin America. The study will adhere to STROBE guidelines for observational research.

Study Population

Eligible participants will include adult patients (≥18 years) presenting with severe trauma and clinical evidence of hemorrhagic shock. Hemorrhagic shock will be defined using a combination of clinical and laboratory criteria, including systolic blood pressure <90 mmHg, elevated lactate levels, base deficit, and/or clinical signs of hypoperfusion.

Inclusion Criteria Adult patients with major trauma (Injury Severity Score ≥15) Evidence of active bleeding or suspected hemorrhagic shock Admission within a defined time window from injury Exclusion Criteria Severe traumatic brain injury requiring strict blood pressure targets Cardiac arrest prior to hospital arrival Pregnant patients Patients with advanced directives limiting care Exposure Definition

Patients will be categorized based on the initial resuscitation strategy:

Delayed resuscitation group: restricted fluid administration prior to hemorrhage control, targeting permissive hypotension (e.g., systolic blood pressure 80-90 mmHg or presence of radial pulse) Immediate resuscitation group: standard aggressive fluid resuscitation aiming to restore normotension Data Collection

Data will be collected prospectively using standardized case report forms and will include:

Demographic characteristics Mechanism and severity of injury Prehospital and emergency department interventions Hemodynamic parameters and laboratory values Volume of fluids and blood products administered Time to hemorrhage control Outcomes Primary Outcome In-hospital mortality Secondary Outcomes 24-hour mortality Blood product utilization Development of complications (e.g., acute respiratory distress syndrome, multiple organ dysfunction syndrome, acute kidney injury) Length of stay in intensive care unit and hospital Need for surgical or interventional procedures Statistical Analysis

Descriptive statistics will be used to summarize baseline characteristics. Comparisons between groups will be performed using appropriate statistical tests (Chi-square, t-test, or Mann-Whitney U test). Multivariable logistic regression models will be constructed to evaluate the association between resuscitation strategy and outcomes, adjusting for potential confounders such as injury severity, age, mechanism of trauma, and comorbidities.

Propensity score methods may be employed to reduce selection bias and improve comparability between groups. Sensitivity analyses will be conducted to assess robustness of findings.

Expected Results

It is hypothesized that delayed resuscitation will be associated with:

Reduced in-hospital mortality Lower transfusion requirements Decreased incidence of complications related to fluid overload and coagulopathy

However, potential risks, including inadequate organ perfusion and adverse outcomes in specific subgroups, will also be critically evaluated.

Enrollment: 716 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Major injuries.
• ISS >15.
• Hypotension with a systolic blood pressure below 90 mmHg.
• No previous hospital care.
• Older than 16 years.

Exclusion criteria

• Brain injuries.
• Pregnancy.
• Drowning.
• Burns.

Trial design

716 participants in 2 patient groups

Delayed resuscitation

Description:

IV fluids lower than 1000 mL.

Treatment:

Drug: Crystalloid below 1000 mL.

Immediate resuscitation

Description:

IV fluids \> 1000 mL

Treatment:

Drug: IV fluids more than 1,000 mL