Sedation for Non-invasive Ventilation in Blunt Chest Trauma

Study Overview
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Brief Summary
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Effectiveness of sedation using dexmedetomidine and ketamine to facilitate non-invasive ventilation sessions which improve overall outcome after blunt chest trauma

Detailed Description
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Chest trauma remains an issue for health services for both severe and apparently mild trauma management. Severe chest trauma is associated with high mortality and is considered liable for 25% of mortality in multiple traumas. Moreover, mild trauma is also associated with significant morbidity especially in patients with preexisting conditions. Thus, whatever the severity, a fast-acting strategy must be organized. Blunt traumas are commonly secondary to motor vehicle accidents, falls, and crush or blast injuries. They are the most common type of thoracic trauma, accounting for over 90%, and are often associated with rib fractures, haemothorax, pneumothorax, and pulmonary contusions. In order to improve the prognosis of patients with severe chest trauma, early and continuous application of non-invasive mechanical ventilation (NIV) can indeed reduce the need for intubation and shorten intensive care unit length-of-stay Among different mechanisms, the early use of positive end-expiratory pressure after chest trauma, when feasible, seems mandatory to optimize oxygenation and improve clinical outcomes. Indeed, interventions aimed at preventing acute respiratory distress syndrome (ARDS) after chest trauma carry the greatest potential to reduce the substantial morbidity, mortality, and resource utilization associated with this syndrome. Notably, pain control seems a crucial endpoint in our success to deliver non-invasive ventilation to patients with chest trauma, when feasible as a pivotal component of patient care after chest trauma, along with non-invasive ventilation. In this context, the role of intensivist doctors is thus to provide optimal control of chest wall pain, respiratory comfort, agitation, and anxiety as a prerequisite to reduce the incidence of NIV failure in this trauma population. In this context, dexmedetomidine could be an alternative to improve NIV tolerance. Dexmedetomidine is a short-acting alpha-2 adrenoreceptor agonist that provides sedation and analgesia with no significant respiratory depression and a reduced risk of delirium. Ketamine has several advantages compared with conventional sedatives such as preserving pharyngeal and laryngeal protective reflexes, lowering airway resistance, increasing lung compliance, and being less likely to produce respiratory depression. It causes sympathetic stimulation, which is also unlike other sedatives and analgesics. However, no studies have estimated the superiority of dexmedetomidine or Ketamine to improve analgesia and non-invasive ventilation tolerance in patients with blunt chest The patients will be randomly allocated into 3 groups, the allocation of the treatment order will determine by means of a computer-generated random table. Group C: will receive placebo infusion (0.9% sodium chloride solution) Group D: will receive dexmedetomidine infusion Group K: will receive ketamine infusion

Official Title
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Dexmedetomidine Versus Ketamine to Facilitate Non-invasive Ventilation After Blunt Chest Trauma

Conditions
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Chest Trauma

Intervention / Treatment
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* Drug: Dexmedetomidine Hydrochloride
* Drug: Ketamine Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All blunt chest trauma patients with: More than 3 rib fractures, pulmonary contusion, hypoxemia or hypercapnia, or respiratory rate 20/ min despite an optimized intravenous analgesia ( paracetamol 1gm i.v. 6hourly and ketolac 30mg i.v. 8 hourly) No indication of mechanical ventilation Exclusion Criteria: Patients < 18 years old, admitted under mechanical ventilation admitted more than 24 h after trauma or from another hospital, patients with less than 3 ribs fractures patients did not receive CT-scan Patients in whom alpha-2 agonists or ketamine are contraindicated Patients who will require an intubation during the study period for a life-threatening condition or emergency surgery or agitation as defined by a Richmond Agitation Sedation Scale (RASS) score higher than +2 will also excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexmedetomidine<br>patients will receive two NIV sessions during which intravenous continuous infusion of dexmedetomidine will be given. The infusion was initiated 60 min prior to NIV at the same rate for all treatments, corresponding to 0.7 mcg/kg/h of dexmedetomidine without a loading dose. Dexmedetomidine will then titrate by 0.2 mcg/kg/h every 60 min (up to a maximum dose of 1.3 mcg/kg/h) to maintain a RASS score between 0 and 3. A 6-h washout period was observed between two NIV sessions accounting for 1-h contextual half-life of dexmedetomidine. Patients received neither tested drug nor NIV during this 6-h interval. | Drug: Dexmedetomidine Hydrochloride<br>* is a sympatholytic drug that acts as an agonist of α2-adrenergic receptors in certain parts of the brain.<br>* Other names: Precedex;|
| Active Comparator: Ketamine<br>patients will receive two NIV sessions during which intravenous continuous infusion of ketamine will be given. The infusion was initiated 60 min prior to NIV at the same rate for all treatments, infusion of ketamine will be at the dose of 0.20 mg/kg/h (or 3.3 mg/kg/min). to maintain a RASS score between 0 and 3. A 6-h washout period was observed between two NIV sessions . Patients received neither tested drug nor NIV during this 6-h interval. Following the start of the infusion, the patient could have a morphine dose if the 10-cm Visual Analog Scale (VAS) exceeded 3. | Drug: Ketamine Hydrochloride<br>* Ketamine is an NMDA receptor antagoni<br>* Other names: Ketalar;|
| Placebo Comparator: Placebo<br>patients will receive two NIV sessions during which intravenous continuous infusion of placebo (0.9% sodium chloride solution) will be given. The infusion was initiated 60 min prior to NIV at the same rate for all treatments, corresponding to 0.7 mcg/kg/h of dexmedetomidine without a loading dose. will then titrate by 0.2 mcg/kg/h every 60 min (up to a maximum dose of 1.3 mcg/kg/h) to maintain a RASS score between 0 and 3. A 6-h washout period was observed between two . Patients received neither tested drug nor NIV during this 6-h interval. Following the start of any infusion, the patient could have a morphine dose if the 10-cm Visual Analog Scale (VAS) exceeded 3. | Drug: Placebo<br>* Normal saline<br>* Other names: Nacl .9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of non-invasive ventilation (NIV) session | duration that patient can withhold NIV comfortably | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Richmond agitation sedation score (RASS) | The hourly measurements by nurses of RASS score for pain and respiratory discomfort during each NIV session. | 8 hours | 
| Visual analogue scale | the hourly measurements of self-rated 10-cm VAS for pain during each NIV session. | 8 hours | 
| length of ICU stay | Through study completion, an average of 1 year | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sedation - noninvasive ventilation-ketamine- dexmedetomidine