cardiovascular-agents and Brain-Injuries

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

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

Distributive shock is defined as circulatory insufficiency induced by excessive dilatation of the peripheral vasculature or maldistribution of cardiac output. Septicemia, systemic inflammatory response syndrome, anaphylaxis, injuries to the central nervous system, and drug intoxication are causative factors of shock. Circulatory derangements induced by bacterial infection have been divided into hyperdynamic and hypodynamic shock. Administration of inotropic drugs, vasopressors, and/or vasodilators are primary treatments in this type of shock. Continuous infusion of norepinephrine to maintain blood pressure or administration of inoptropes such as dopamine or dobutamine are recommended to improve tissue perfusion. High-dose intravenous epinephrine is required to reestablish cardiac function, followed by continuous infusion of norepinephrine in severe anaphylactic shock. Vasoconstrictors such as norepinephrine, vasopressin, or amaminone are administered to maintain vascular tone in shock caused by nerve damage or drug overdose.

Topics: Anaphylaxis; Brain Injuries; Cardiovascular Agents; Dopamine; Epinephrine; Humans; Norepinephrine; Sepsis; Shock; Spinal Cord Injuries; Vascular Resistance

Acute, severe increases in arterial blood pressure cause sustained cerebral arteriolar dilation, abnormal reactivity to carbon dioxide and to changes in blood pressure, abolition of endothelium-dependent dilation from acetylcholine, discrete morphological lesions of the endothelium and vascular smooth muscle, and breakdown of the blood-brain barrier to plasma proteins. The dilation, abnormal reactivity, and morphological abnormalities are inhibited by pretreatment with cyclooxygenase inhibitors or with free radical scavengers. Superoxide dismutase-inhibitable reduction of nitroblue tetrazolium applied to the brain surface was detectable both during hypertension and one hour after hypertension subsided. Nitroblue tetrazolium reduction is also reduced by inhibitors of the anion channel. The abnormalities seen after hypertension are reproduced by topical application of arachidonate. The results are consistent with the view that acute hypertension induces generation of superoxide anion radical in association with accelerated arachidonate metabolism via cyclooxygenase. This radical enters cerebral extracellular space via the anion channel and gives rise to hydrogen peroxide and hydroxyl radical. All three radicals are capable of causing vasodilation by relaxation of cerebral vascular smooth muscle. The hydroxyl radical is the most likely candidate for vascular wall damage. The significance of this mechanism in chronic experimental hypertension or its relevance to human disease is not known.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Arterioles; Blood Proteins; Blood-Brain Barrier; Bradykinin; Brain; Brain Injuries; Cardiovascular Agents; Catalase; Cerebrovascular Circulation; Cerebrovascular Disorders; Cyclooxygenase Inhibitors; Endothelium; Free Radicals; Hydrogen Peroxide; Hydroxides; Hydroxyl Radical; Hypertension; Leukocytes; Leukotrienes; Lipid Peroxides; Muscle, Smooth, Vascular; Peroxidases; Prostaglandin-Endoperoxide Synthases; Prostaglandins G; Superoxide Dismutase; Superoxides; Vasodilation; Xanthine Oxidase

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

Traumatic brain injury (TBI) is a leading cause of morbidity in children and boys are disproportionately represented. Hypotension is common and worsens outcome after TBI. Previous studies show that adrenomedullin, a cerebrovasodilator, prevented sex dependent impairment of autoregulation during hypotension after piglet fluid percussion brain injury (FPI). We hypothesized that this concept was generalizable and that administration of another vasodilator, sodium nitroprusside (SNP), may equally improve CBF and cerebral autoregulation in a sex dependent manner after FPI. SNP produced equivalent percent cerebrovasodilation in male and female piglets. Reductions in pial artery diameter, cortical CBF, and cerebral perfusion pressure (CPP) concomitant with elevated intracranial pressure (ICP) after FPI were greater in male compared to female piglets during normotension which was blunted by SNP. During hypotension, pial artery dilation (PAD) was impaired more in the male than the female after FPI. However, SNP did not improve hypotensive PAD after FPI in females and paradoxically caused vasoconstriction in males. SNP did not prevent reductions in CBF, CPP or autoregulatory index during combined hypotension and FPI in either sex. SNP aggravated ERK MAPK upregulation after FPI. These data indicate that despite prevention of reductions in CBF after FPI, SNP does not prevent impairment of autoregulation during hypotension after FPI. These data suggest that therapies directed at a purely hemodynamic increase in CPP will fail to improve outcome during combined TBI and hypotension.

Topics: Animals; Animals, Newborn; Arteries; Brain; Brain Injuries; Cardiovascular Agents; Cerebrovascular Circulation; Extracellular Signal-Regulated MAP Kinases; Female; Intracranial Hypotension; Male; MAP Kinase Signaling System; Nitroprusside; Pia Mater; Sex Characteristics; Swine; Time Factors

Ventilator-associated pneumonia is a familiar foe in intensive care units, but those associated with Pseudomonas aeruginosa have a particularly adverse impact on outcome. Correct antibiotic therapy and a novel endotracheal tube may reduce this burden. Does activated protein C improve outcome from acute lung injury and what is the role played by hyperventilation therapy in traumatic brain injury? Recent research has attempted to answer these questions. Further novel approaches have been evaluated in the management of ischaemic heart disease, and more light has been shed on acute bowel injury.

Topics: Brain Injuries; Cardiovascular Agents; Gastrointestinal Diseases; Humans; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections

A comprehensive otoneurological investigation of 131 patients with head injuries of shoch-wave and mechanical nature has revealed similar acoustic, vestibular and central hemodynamic disorders in the above patients. The diagnosed pathological features are determined only by strength and extention of the traumatic factor but not by its nature. Common features in development of acoustic and vestibular disorders in patients with different head injuries enable design of an integrated therapeutic and diagnostic algorithm of management of the above patients with the drugs tanakan and gincor fort.

Topics: Adolescent; Adult; Audiometry, Evoked Response; Auditory Pathways; Blast Injuries; Brain Injuries; Cardiovascular Agents; Female; Ginkgo biloba; Hearing Loss; Hearing Loss, Noise-Induced; Humans; Male; Middle Aged; Plant Extracts; Severity of Illness Index; Vestibule, Labyrinth

Vomiting, abdominal distension, and feeding intolerance are common findings following brain injury in children, and are usually attributed to the brain injury or to delayed gastric emptying: a specific cause is usually not sought. We report six children who developed mild to moderate pancreatitis at least 7 days following apparently isolated brain injury, a previously unreported association. Five of the six patients received drugs that are known or suspected pancreatotoxins; all recovered without changes in the medications. When children develop feeding intolerance or upper gastrointestinal symptoms following traumatic brain injury pancreatitis should be suspected.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Anticonvulsants; Brain Injuries; Cardiovascular Agents; Child; Child, Preschool; Female; Head Injuries, Closed; Hematoma, Subdural; Humans; Male; Pancreatitis; Psychotropic Drugs; Risk Factors; Wounds, Gunshot

Over the past 15 years, neuropathological studies, patient monitoring, and data emerging from the laboratory have significantly advanced the understanding of both primary and secondary brain damage. The challenge now rests with the clinician treating head injury, who must translate these recent developments into real benefits for the patient. Neurological deterioration after head injury may be due to the effects of secondary mechanisms in up to one-third of cases. These secondary events may follow early insults such as transient global ischemia, hematomas, or diffuse axonal injury. They may be mediated by complex cascades of biochemical processes. Many of these secondary posttraumatic events have been targeted as potential sites for pharmacological intervention. In models of focal brain ischemia, a new generation of compounds that inhibit activity of glutamate has been shown to ameliorate the severity of the ischemic insult. Other potential neuroprotective agents that are currently being clinically investigated include free radical scavengers and calcium antagonists. Preliminary findings show indications of improved neurological outcome with early administration of a number of these drugs. Because head-injured patients tend to be admitted to the hospital within hours of injury, which allows for pretreatment or early therapy, several ongoing trials are assessing safety, tolerance, and efficacy of many new therapeutic agents combined with standard management. It is hoped that the outcome of this novel approach to head injury management will be positive and will help to reduce the high morbidity and mortality associated with head injuries.

Topics: Animals; Brain Chemistry; Brain Injuries; Cardiovascular Agents; Diuretics; Drug Therapy, Combination; Growth Substances; Hematoma, Subdural; Humans; Hypnotics and Sedatives; Intracranial Pressure; Methylprednisolone; Rats

Topics: Anesthesia; Anesthesia, Conduction; Anesthesiology; Autonomic Nerve Block; Brain; Brain Injuries; Cardiovascular Agents; Ergot Alkaloids; Humans

Topics: Brain; Brain Concussion; Brain Injuries; Cardiovascular Agents; Ergot Alkaloids; Humans; Oxytocics; Wounds and Injuries