Ignite Creation Date:
2024-05-06 @ 4:58 PM
Last Modification Date:
2024-10-26 @ 2:19 PM
Study NCT ID:
NCT05149586
Status:
COMPLETED
Last Update Posted:
2023-05-01
First Post:
2021-11-24
Brief Title:
Impact of Low Dose Ketamine Infusion in Septic Patient on Non-invasive Estimators of ICP
Sponsor:
Zagazig University
Organization:
Zagazig University
Study Overview
Official Title:
Principle Investigator
Status:
COMPLETED
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Severe sepsis is a major healthcare problem with a reported incidence of 1-2 in all hospitalizations It is a major cause of death in the intensive care units worldwide and is the second leading cause of death in noncoronary intensive care unit patients Mortality remains high at 30-50 despite a better understanding of sepsis pathophysiology and improved advanced care in the past decade
Sedation and analgesia in the intensive care unit ICU for patients with sepsis and tenuous hemodynamics can be challenging Opioids and benzodiazepines can contribute to the pathophysiology of shock by exacerbating poor tissue perfusion through reduced cardiac contractility and increased vasodilation as well as reducing the respiratory drive
Sedation and analgesia management are both integral components of care in the intensive care unit ICU Although benzodiazepines have been the mainstay therapy for sedation in critically ill patients their use has declined in recent years with favoring of nonbenzodiazepinessuch as propofol and dexmedetomidine
A noticeable interest in ketamine infusion for sedation management in critically ill patients has developed among critical care physicians The 2018 Pain Agitation sedation Delirium Immobility and Sleep disruption PADIS guideline suggested low-dose ketamine as an adjunct to opioid therapy for reducing opioid consumption in post-surgical adults admitted to the ICU
Ketamine affects many pathways leading to inflammation cascade during sepsis First ketamine has an immunosuppressive effect on immune cells such as NK cell cytotoxic activity neutrophil adhesion to endothelium and chemotactic activity of neutrophils Second ketamine decreases Toll-like receptor expression nuclear factorkB activity and RafRaf cascade Third ketamine suppresses cytokines superoxide and nitric oxide productions and reduces the mitochondrial membrane potential in macrophages Finally ketamine prevents the alteration of immune function in patients early after a major surgery and increases survival in rats with sepsis
Cerebral perfusion pressure CPP was compromised only in the patients with pre-existing intracranial hypertension and obstruction to the flow of cerebral spinal fluid This has however led to the persistent belief that ketamine is contraindicated in patients with traumatic head injuries Studies done subsequently have shown however that the effects of ketamine on cerebral haemodynamics and ICP are in fact variable and depend on both the presence of additional anaesthetic agents and PaCO2 values Meta-analysis also suggests that Ketamine does not increase ICP and provides favorable hemodynamics Meta analysis has shown that when ketamine is used in the presence of controlled ventilation in conjunction with anaesthetics which reduce cerebral metabolism such as GABA receptor agonists ICP is not increased
The gold standard technique for ICP measurement is an intraventricular catheter10 however this method is invasive and can have complications Non-invasive ICP nICP measurement is a promising technique still under development in adult and pediatric population Optic nerve sheath diameter ONSD measurement using ocular ultrasonography is a safe quick reliable and reproducible technique for the assessment of ICP Transcranial Doppler Ultrasonography TCD can also non-invasively assess ICP and CPP Increased ICP produces characteristic changes in cerebral blood flow velocity FV waveform that can be assessed by decreases in the diastolic FV and increases in the pulsatility index PIsystolic FV - diastolic FV mean FV and several methods TCD derived have been proposed to assess non invasively ICP showing good performance
Sepsis-associated encephalopathy SAE usually manifests as sleep awakening cycle disturbance cognitive impairment delirium and coma Considering that brain edema secondary to SAE is one of the complications and causes of death in patients with sepsis early detection of intracranial hypertension ICH is of great significance for timely intervention and improved prognosis However most patients with sepsis without intracranial infection have no indications for invasive intracranial pressure ICP monitoring thus non-invasive ICP monitoring was selected
Therefore in patients without invasive ICP monitoring nICP methods may be useful for determining if ketamine infusion in septic patient will cause a pathological increase in ICP
Sedation and analgesia in the intensive care unit ICU for patients with sepsis and tenuous hemodynamics can be challenging Opioids and benzodiazepines can contribute to the pathophysiology of shock by exacerbating poor tissue perfusion through reduced cardiac contractility and increased vasodilation as well as reducing the respiratory drive
Sedation and analgesia management are both integral components of care in the intensive care unit ICU Although benzodiazepines have been the mainstay therapy for sedation in critically ill patients their use has declined in recent years with favoring of nonbenzodiazepinessuch as propofol and dexmedetomidine
A noticeable interest in ketamine infusion for sedation management in critically ill patients has developed among critical care physicians The 2018 Pain Agitation sedation Delirium Immobility and Sleep disruption PADIS guideline suggested low-dose ketamine as an adjunct to opioid therapy for reducing opioid consumption in post-surgical adults admitted to the ICU
Ketamine affects many pathways leading to inflammation cascade during sepsis First ketamine has an immunosuppressive effect on immune cells such as NK cell cytotoxic activity neutrophil adhesion to endothelium and chemotactic activity of neutrophils Second ketamine decreases Toll-like receptor expression nuclear factorkB activity and RafRaf cascade Third ketamine suppresses cytokines superoxide and nitric oxide productions and reduces the mitochondrial membrane potential in macrophages Finally ketamine prevents the alteration of immune function in patients early after a major surgery and increases survival in rats with sepsis
Cerebral perfusion pressure CPP was compromised only in the patients with pre-existing intracranial hypertension and obstruction to the flow of cerebral spinal fluid This has however led to the persistent belief that ketamine is contraindicated in patients with traumatic head injuries Studies done subsequently have shown however that the effects of ketamine on cerebral haemodynamics and ICP are in fact variable and depend on both the presence of additional anaesthetic agents and PaCO2 values Meta-analysis also suggests that Ketamine does not increase ICP and provides favorable hemodynamics Meta analysis has shown that when ketamine is used in the presence of controlled ventilation in conjunction with anaesthetics which reduce cerebral metabolism such as GABA receptor agonists ICP is not increased
The gold standard technique for ICP measurement is an intraventricular catheter10 however this method is invasive and can have complications Non-invasive ICP nICP measurement is a promising technique still under development in adult and pediatric population Optic nerve sheath diameter ONSD measurement using ocular ultrasonography is a safe quick reliable and reproducible technique for the assessment of ICP Transcranial Doppler Ultrasonography TCD can also non-invasively assess ICP and CPP Increased ICP produces characteristic changes in cerebral blood flow velocity FV waveform that can be assessed by decreases in the diastolic FV and increases in the pulsatility index PIsystolic FV - diastolic FV mean FV and several methods TCD derived have been proposed to assess non invasively ICP showing good performance
Sepsis-associated encephalopathy SAE usually manifests as sleep awakening cycle disturbance cognitive impairment delirium and coma Considering that brain edema secondary to SAE is one of the complications and causes of death in patients with sepsis early detection of intracranial hypertension ICH is of great significance for timely intervention and improved prognosis However most patients with sepsis without intracranial infection have no indications for invasive intracranial pressure ICP monitoring thus non-invasive ICP monitoring was selected
Therefore in patients without invasive ICP monitoring nICP methods may be useful for determining if ketamine infusion in septic patient will cause a pathological increase in ICP
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None