cardiovascular-agents and Intracranial-Hypertension

Among people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury.. To assess the effects of indomethacin for adults with severe traumatic brain injury.. We ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field.. Our search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery.. Two review authors independently decided on the selection of the studies. We followed standard Cochrane methods.. We identified no eligible studies for this review, either completed or ongoing.. We found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review.

Topics: Brain Injuries, Traumatic; Cardiovascular Agents; Humans; Indomethacin; Intracranial Hypertension; Intracranial Pressure; Randomized Controlled Trials as Topic

Our goal was to perform a systematic review of the literature on the use of indomethacin and its effects on intracranial pressure (ICP) in patients with neurological illness. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to July 2014), reference lists of relevant articles, and gray literature were searched. Two reviewers independently identified all manuscripts utilizing the following inclusion and exclusion criteria.. Humans, prospective studies (five or more patients), documented ICP response to indomethacin, and English.. non-English, retrospective studies, no documentation of ICP response to indomethacin, and animal studies. A two-tier filter of references was conducted. First, we screened manuscripts by title and abstract. Second, those references passing the first filter were pulled, and the full manuscript was checked to see if it matched the criteria for inclusion. Two reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total of 208 citations. Twelve original articles, 10 manuscripts, and 2 meeting proceeding, were considered for the review with all utilizing indomethacin, while documenting ICP in neurological patients. All studies were prospective. Across all studies, there were a total of 177 patients studied, with 152 receiving indomethacin and 25 serving as controls in a variety of heterogeneous studies. All but one study documented a decrease in ICP with indomethacin administration, with both bolus and continuous infusions. No significant complications were described. There currently exists Oxford level 2b, GRADE C evidence to support that indomethacin reduces ICP in the severe TBI population. Similar conclusions in other populations cannot be made at this time. Comments on its impact, on patient outcome, and side effects cannot be made given the available data. At this time, indomethacin for ICP control remains experimental and further prospective study is warranted.

Topics: Brain Injuries; Cardiovascular Agents; Humans; Indomethacin; Intracranial Hypertension

Severe intracranial hypertension (IH) in the setting of fulminant hepatic failure (FHF) carries a high mortality and is a challenging disease for the critical care provider. Despite considerable improvements in the understanding of the pathophysiology of cerebral edema during liver failure, therapeutic maneuvers that are currently available to treat this disease are limited. Orthotopic liver transplantation is currently the only definitive therapeutic strategy that improves outcomes in patients with FHF. However, many patients die prior to the availability of donor organs, often because of cerebral herniation. Currently, two important theories prevail in the understanding of the pathophysiology of IH during FHF. Ammonia and glutamine causes cytotoxic cerebral injury while cerebral vasodilation caused by loss of autoregulation increases intracranial pressure (ICP) and predisposes to herniation. Although ammonia-reducing strategies are limited in humans, modulation of cerebral blood flow seems promising, at least during the early stages of hepatic encephalopathy. ICP monitoring, transcranial Doppler, and jugular venous oximetry offer valuable information regarding intracranial dynamics. Induced hypothermia, hypertonic saline, propofol sedation, and indomethacin are some of the newer therapies that have been shown to improve survival in patients with severe IH. In this article, we review the pathophysiology of IH in patients with FHF and outline various therapeutic strategies currently available in managing these patients in the critical care setting.

Topics: Ammonia; Anesthetics, Intravenous; Brain; Cardiovascular Agents; Cerebrovascular Circulation; Electroencephalography; Glutamine; Humans; Hyperventilation; Hypothermia, Induced; Indomethacin; Intracranial Hypertension; Liver Failure, Acute; Propofol; Vasodilation

The management of severe head injuries in general and that of high intracranial pressure (ICP) in particular are among the most challenging tasks in neurocritical care. One of the difficulties still faced by clinicians is that of reducing variability among centers when implementing management protocols. The purpose of this paper is to propose a standardized protocol for the management of high ICP after severe head injury, consistent with recently published clinical practice guidelines and other clinical evidence such as that provided by the systematic reviews of the Cochrane Collaboration. Despite significant advances in neuromonitoring, deeper insight into the physiopathology of severe brain trauma and the many therapeutic options available, standardized protocols are still lacking. Recently published guidelines provide sketchy recommendations without details on how and when to apply different therapies. Consequently, great variability exists in daily clinical practice even though different centers apply the same evidence-based recommendations. In this paper we suggest a structured protocol in which each step is justified and integrated into an overall strategy for the management of severe head injuries. The most recent data from both the preliminary and definitive results of randomized clinical trials as well as from other sources are discussed. The main goal of this article is to provide neurotraumatology intensive care units with a unified protocol that can be easily modified as new evidence becomes available. This will reduce variation among centers when applying the same therapeutic measures. This goal will facilitate comparisons in outcomes among different centers and will also enable the implementation of more consistent clinical practice in centers involved in multicenter clinical trials.

Topics: Adrenal Cortex Hormones; Analgesics; Anticonvulsants; Brain Edema; Brain Injuries; Calcium Channel Blockers; Cardiovascular Agents; Case Management; Combined Modality Therapy; Craniocerebral Trauma; Critical Care; Electrophysiology; Evidence-Based Medicine; Fluid Therapy; Hemodynamics; Humans; Hypnotics and Sedatives; Intracranial Hypertension; Monitoring, Physiologic; Neuromuscular Nondepolarizing Agents; Practice Guidelines as Topic; Seizures

Increased intracranial pressure (ICP) is a pathological state common to a variety of neurological diseases, all of which are characterized by the addition of volume to the skull contents. Elevated ICP may lead to brain damage or death by two principle mechanisms: 1) global hypoxic-ischemic injury, as a consequence of reduced cerebral perfusion pressure (CPP) and cerebral blood flow; and 2) mechanical distortion and compression of brain tissue as a result of intracranial mass effect and ICP compartmentalization. All ICP therapies have as a goal, reduction of intracranial volume. In unmonitored patients with acute neurological deterioration, head elevation, hyperventilation, and mannitol (1g/kg) can rapidly lower ICP. Fluid-coupled ventricular catheters and fiberoptic transducers are the most accurate and reliable instruments for measuring ICP. In monitored patients, the treatment of critically raised ICP should proceed in an orderly step-wise fashion: 1) consideration of neuroimaging to exclude a new surgically operable lesion; 2) intravenous sedation to attain a quiet motionless state; 3) manipulation of blood pressure to keep CPP >70 and <120; 4) mannitol infusion; 5) moderate hyperventilation (P(CO2) 26 to 30 mmHg); and 6) high-dose pentobarbital therapy. Application of moderate hypothermia (32 to 33 degrees C) shows promise as a newer method for treating refractory ICP. Placement of an ICP monitor is the critical first step in management of ICP. Treatment is best done using a stepwise protocol, with careful attention to sedation and CPP control prior to using mannitol and hyperventilation.

Topics: Blood Pressure; Cardiovascular Agents; Diuretics, Osmotic; Humans; Hyperventilation; Hypnotics and Sedatives; Intracranial Hypertension; Mannitol

Intracranial hypertension is the final pathway of many neurocritical entities, such as spontaneous intracerebral hemorrhage (sICH) and severe traumatic brain injury (sTBI).. This study aimed to (1) determine alterations in intracranial pressure (ICP) and cerebral hemodynamics after an indomethacin (INDO) infusion test and the related association with survival in patients with refractory intracranial hypertension (RICH) secondary to sICH or sTBI and (2) assess the safety profile after INDO.. INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by a 2-hour continuous infusion (0.5 mg/kg/h) in RICH patients with ICP greater than 20 mm Hg who did not respond to first-line therapies. Changes in ICP, cerebral perfusion pressure (CPP), and cerebrovascular variables (assessed by transcranial Doppler and jugular bulb saturation) were observed. Clinical outcome was assessed at 1 and 6 months according to the Glasgow Outcome Scale and correlated with INDO infusion test response. Analysis of INDO safety profile was conducted.. Thirteen sICH and 10 sTBI patients were studied. The median GCS score at admission was 6. Within 30 minutes of INDO infusion, ICP decreased (42.0 ± 13.5 vs 27.70 ± 12.7 mm Hg; Δ%: -48.4%; P < .001), and both CPP (57.7 ± 4.8 vs 71.9 ± 7.0 mm Hg; Δ%: +26.0%; P < .001) and middle cerebral artery velocity (35.2 ± 5.6 vs 42.0 ± 5.1 cm·s(-1); Δ%: +26.1%; P < .001) increased. The CPP response to a 2-hour INDO infusion test was correlated (R2 = 0.72, P < .001) with survival. No adverse events were observed after INDO.. Our findings support the effectiveness and feasibility of an INDO test in decreasing ICP and improving cerebral hemodynamics in surviving RICH patients. Future studies to evaluate different doses, lengths of infusion, and longer term effects are needed.

Topics: Adult; Aged; Antihypertensive Agents; Cardiovascular Agents; Cerebrovascular Circulation; Chronic Disease; Feasibility Studies; Female; Humans; Indomethacin; Intracranial Hypertension; Intracranial Pressure; Male; Sensitivity and Specificity; Treatment Outcome

Recently, a concept of an individually targeted level of cerebral perfusion pressure that aims to restore impaired cerebral vasoreactivity has been advocated after traumatic brain injury. The relationship between cerebral perfusion pressure and pressure reactivity index normally is supposed to have a U-shape with its minimum interpreted as the value of "optimal" cerebral perfusion pressure. The aim of this study is to investigate the relation between the absence of the optimal cerebral perfusion pressure curve and physiological variables, clinical factors, and interventions.. Retrospective analysis of prospectively collected data.. Neurocritical care units in two university centers.. Between May 2012 and December 2013, a total of 48 traumatic brain injury patients were studied with real-time annotation of predefined clinical events.. None.. All patients had continuous monitoring of arterial blood pressure, intracranial pressure, and cerebral perfusion pressure, with real-time calculations of pressure reactivity index and optimal cerebral perfusion pressure using ICM+ software (Cambridge Enterprise, University of Cambridge, Cambridge, UK). Selected clinical events were inserted on a daily basis, including changes in physiological variables, sedativeanalgesic drugs, vasoactive drugs, and medical/surgical therapies for intracranial hypertension. The collected data were divided into 4-hour periods, with the primary outcome being absence of the optimal cerebral perfusion pressure curve. For every period, mean values (± SDs) of arterial blood pressure, intracranial pressure, pressure reactivity index, and other physiological variables were calculated; clinical events were organized using predefined scales. In 28% of all 1,561 periods, an optimal cerebral perfusion pressure curve was absent. A generalized linear mixed model with binary logistic regression was fitted. Absence of slow arterial blood pressure waves (odds ratio, 2.7; p < 0.001), higher pressure reactivity index values (odds ratio, 2.9; p < 0.001), lower amount of sedative-analgesic drugs (odds ratio, 1.9; p = 0.03), higher vasoactive medication dose (odds ratio, 3.2; p = 0.02), no administration of maintenance neuromuscular blockers (odds ratio, 1.7; p < 0.01), and following decompressive craniectomy (odds ratio, 1.8; p < 0.01) were independently associated with optimal cerebral perfusion pressure curve absence.. This study identified six factors that were independently associated with absence of optimal cerebral perfusion pressure curves.

Topics: Adult; Analgesics; Brain; Brain Injuries; Cardiovascular Agents; Cerebrovascular Circulation; Female; Glasgow Coma Scale; Humans; Hypnotics and Sedatives; Intracranial Hypertension; Intracranial Pressure; Male; Middle Aged; Retrospective Studies

Refractory intracranial hypertension (RICH) is associated with high mortality in severe traumatic brain injury (sTBI). Indomethacin (INDO) can decrease intracranial cerebral pressure (ICP) improving cerebral pressure perfusion (CPP). Our aim was to determine modifications in ICP and CPP following INDO in RICH secondary to sTBI.. INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by continuous 2-h infusion period (0.5 mg/kg/h). Clinical outcome was assessed at 30 days according to Glasgow Outcome Scale (GOS). Differences in ICP and CPP values were assessed using repeated-measures ANOVA. Receiver operating characteristic curve (AUC) was used for discrimination in predicting 30-day survival and good functional outcome (GOS 4 or 5). Analysis of INDO safety profile was also conducted.. Thirty-two patients were included. Median GCS score was 6 (interquartile range: 4-7). The most frequent CT finding was the evacuated mass lesion (EML) according to Marshall classification (28.1 %). Mortality rate was 34.4 %. Within 15 min of INDO infusion, ICP decreased (Δ%: -54.6 %; P < 0.0001), CPP increased (Δ%: +44.0 %; P < 0.0001), and the remaining was stable during the entire infusion period. Patients with good outcome (n = 12) showed a greater increase of CPP during INDO test (P = 0.028). CPP response to INDO test discriminated moderately well surviving patients (AUC = 0.751; P = 0.0098) and those with good functional recovery (AUC = 0.763; P = 0.0035) from those who died and from those with worse functional outcome, respectively. No adverse events were observed.. INDO appears effective in reducing ICP and improving CPP in RICH. INDO test could be a useful tool in identifying RICH patients with favorable outcome. Future studies are needed.

Topics: Adolescent; Adult; Aged; Brain Injuries; Cardiovascular Agents; Cerebrovascular Circulation; Glasgow Outcome Scale; Humans; Indomethacin; Intracranial Hypertension; Intracranial Pressure; Male; Middle Aged; Treatment Outcome; Young Adult

Topics: Acute Disease; Brain Edema; Brain Ischemia; Cardiovascular Agents; Case Management; Combined Modality Therapy; Decompression, Surgical; Fever; Humans; Hyperglycemia; Hypertension; Hypoxia; Intracranial Hypertension; Pneumonia; Thrombolytic Therapy; Urinary Tract Infections; Water-Electrolyte Imbalance