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Michael N Diringer

Publications and source records attributed to Michael N Diringer.

At least 19 recordsLinked to original sources
PubMed2006

Safety and technical efficacy of over-the-wire balloons for the treatment of subarachnoid hemorrhage-induced cerebral vasospasm.

OBJECT: Over the past decade, low-pressure, flow-directed balloons have been replaced by over-the-wire balloons in the treatment of vasospasm induced by subarachnoid hemorrhage (SAH). The authors assess the procedural safety and technical efficacy of these newer devices. METHODS: Seventy-five patients who underwent 85 balloon angioplasty procedures for the treatment of SAH-induced vasospasm were identified from a prospective quality-assurance database. Medical records and angiographic reports were reviewed for evidence of procedural complications and technical efficacy. No vessel rupture or perforation occurred, but thromboembolic complications were noted in four (4.7%) of the 85 procedures. Balloon angioplasty was frequently attempted and successfully accomplished in the distal internal carotid (100%), proximal middle cerebral (94%), vertebral (73%), and basilar (88%) arteries. Severe narrowing was present in 89 proximal anterior cerebral arteries. Angioplasty was attempted in 41 of these vessels and was successful in only 14 (34%). In 19 of the 27 unsuccessful attempts, the balloon could not be advanced over the wire due to severe vasospasm or unfavorable vessel angle. Follow-up angiography in a subset of patients demonstrated that severe recurrent vasospasm occurred in 15 (13%) of 116 vessels studied after angioplasty. CONCLUSIONS: Over-the-wire balloons involve a low risk for vessel rupture. The anterior cerebral artery remains difficult to access and successfully treat with current devices. Further improvements in balloon design, such as smaller inflated diameters and better tracking, are necessary. Finally, thromboembolic complications remain an important concern, and severe vasospasm may recur after balloon angioplasty.

Adolescent↗
PubMed2006

Effect of intraarterial papaverine and/or angioplasty on the cerebral veins in patients with vasospasm after subarachnoid hemorrhage due to ruptured intracranial aneurysms.

OBJECT: The goal in this study was to determine if there was a change in intracranial venous diameters after endovascular treatment of carotid distribution vasospasm caused by subarachnoid hemorrhage. METHODS: The venous diameters were measured in all patients who received intraarterial papaverine and/or balloon angioplasty for treatment of vasospasm during the study period of 3 years. To evaluate the veins of Labbe and Trolard, the straight sinus, and the superior sagittal sinus (SSS), measurements were performed in a blinded manner with the aid of a magnification loupe. Predetermined sites were evaluated on angiograms obtained before and after endovascular treatment. Forty-three treatments in 26 patients were included: 18 patients (33 territories) were treated with intraarterial papaverine alone, four (four territories) were treated with balloon angioplasty alone, and four (six territories) were treated with both papaverine infusion and angioplasty. The mean measured venous diameters increased significantly after addition of papaverine (10.9%), and also after combined papaverine and angioplasty (4.2%). There was no statistically significant increase in the mean venous diameters after angioplasty alone. If the initial intracranial pressure (ICP) was less than 15 mm Hg before treatment, the veins showed a greater tendency to dilate than if the initial ICP measurements were greater than 15 mm Hg. The straight sinus and the SSS increased more in diameter than the veins of Labbe and Trolard. There was no statistically significant correlation between the change in venous diameters with treatment and ICP. CONCLUSIONS: Endovascular treatment produces measurable increases in intracranial venous diameters. However, these changes do not correlate with changes in ICP.

Adult↗
PubMed2006

Perihematomal mitochondrial dysfunction after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Recent measurements in intracerebral hemorrhage (ICH) patients suggest a primary reduction in brain metabolism is responsible for reduced cerebral blood flow and low oxygen extraction surrounding the hematoma. We sought to determine whether reduced mitochondrial respiratory function could account for reduced metabolic demand in ICH patients. METHODS: Brain-tissue samples from 6 patients with acute spontaneous ICH and 6 control patients undergoing brain resection for management of seizure were evaluated. Only tissue removed from the brain adjacent to the hematoma was studied. Specimens were collected in the operating room; mitochondrial studies were begun within 1-hour. Mitochondrial oxygen consumption was measured after the addition of pyruvate, malate, and ADP, followed by oligomycin and carbonylcyanide. RESULTS: The ICH patients ranged in age from 40 to 54 years; 2 were female and half black. Hemorrhages were located in the temporal lobe (3), cerebellum (2) and parietal lobe (1). The average State 3 (active) O2 consumption for mitochondria from ICH patients was approximately 40% lower than that of control patients ( CONTROLS: 129+/-39 versus ICH: 76+/-28 nmol O2/min per mg protein). With increasing time from hemorrhage to testing there was a progressive decline in State 3 respiration. Reduced State 3 respiration was evident even at 6 hours, whereas at 72 hours, there was essentially no O2 consumption. CONCLUSIONS: These data support the hypothesis that mitochondrial dysfunction and not ischemia is responsible for reduced oxygen metabolism in ICH. They point to a new direction for investigation and development of therapeutic interventions for ICH patients.

Adenosine Triphosphate↗
PubMed2006

Elevated troponin levels are associated with higher mortality following intracerebral hemorrhage.

BACKGROUND: Elevated troponin levels are an independent indicator of poor outcome in ischemic stroke. The authors performed a retrospective study to ascertain whether elevated cardiac troponin I (cTnI) influences outcome from intracerebral hemorrhage (ICH). METHODS: Patients were included if they had a cTnI level measured and a head CT performed within 24 hours of presentation with a spontaneous ICH. Those with recent stroke, angina, or myocardial ischemia were excluded. CT scans were reviewed to determine the hematoma size, location, presence of intraventricular or subarachnoid hemorrhage, hydrocephalus, and midline shift. RESULTS: Of the 729 ICH patients admitted over 4 years, 235 were included in the analysis. Most exclusions were for medical reasons or because of lack of a CT. Mortality was higher in the 18% with a peak cTnI level > 0.4 ng/mL (58 vs 34%, p = 0.009) and having elevated cTnI was an independent predictor of in-hospital mortality (Exp [beta] 3.68, 95% CI 1.2 to 11.2, p = 0.023). Three patients (1.2%) died due to cardiac events, all of whom had an elevated cTnI level on admission. CONCLUSIONS: Elevated cardiac troponin I (cTnI) values occur frequently in ICH and are independently associated with higher in-hospital mortality. Although cardiac causes of death were higher in those with elevated cTnI levels, due to its very low frequency (1.2%) this finding remains preliminary.

Adult↗
PubMed2006

Hypernatremia in the neurologic intensive care unit: how high is too high?

Hypernatremia is associated with increased mortality in hospitalized patients and in medical/surgical intensive care units. This relationship has not been studied in neurologic/neurosurgical intensive care units (NNICUs), where hypernatremia is often a component of treatment of cerebral edema. We performed a retrospective analysis of prospectively collected data in patients admitted to the NNICU over a 6.5-year period. Hypernatremia (serum sodium >150 mEq/L) was seen in 339 patients (7.9%) and was more common (24.3%) in patients who were treated with mannitol. Hypernatremic patients had a lower median admission Glasgow Coma Scale score (8 vs 14, P < .001), higher initial Acute Physiology and Chronic Health Evaluation II probability of death (34.9% vs 19.1%, P < .001), higher incidence of mechanical ventilation (80.5% vs 41.1.5%, P < .001), higher mortality (30.1% vs 10.2%, P < .001), and higher incidence of renal failure (10.3% vs 0.9%, P < .001). Mortality increased with increasing hypernatremia; however, only severe hypernatremia (serum sodium >160 mEq/L) was independently associated with increased mortality. Other factors independently associated with mortality were age, mechanical ventilation, initial Acute Physiology and Chronic Health Evaluation II probability of death or low admission Glasgow Coma Scale score, and a diagnosis of cerebrovascular disease. In conclusion, hypernatremia is common in the NNICU, more so in patients treated with mannitol. In this population, severe (but not mild or moderate) hypernatremia is independently associated with increased mortality.

Adult↗
PubMed2006

Hyponatremia in neurologic patients: consequences and approaches to treatment.

BACKGROUND: Hyponatremia is a common fluid-electrolyte disturbance, particularly in patients with neurologic disorders, in part because of the major role the central nervous system (CNS) plays in the regulation of sodium and water homeostasis. REVIEW SUMMARY: The classification of hyponatremia is based on an assessment of serum sodium concentration ([Na+]), serum and urine osmolality, and body volume status. In most cases, hyponatremia is associated with hypotonicity, which causes water to move into the brain. Adaptive responses limit the impact of cerebral edema in chronic hyponatremia, but CNS symptoms and death may occur in response to rapid or large decreases in serum [Na+]. The prompt correction of serum [Na+] is mandatory in symptomatic patients, but overly rapid correction must be avoided to limit the risk of myelinolysis. In neurologic disorders, euvolemic hyponatremia (usually caused by the syndrome of inappropriate secretion of antidiuretic hormone) must be distinguished from hypovolemic states such as cerebral salt wasting because the treatment of the 2 conditions differs. Vasopressin antagonists represent a new approach to the treatment of euvolemic and hypervolemic hyponatremia secondary to arginine vasopressin dysregulation. CONCLUSION: The optimal treatment of hyponatremia is controversial, but appropriate treatment must be determined according to the osmolality and volume status of the patient. If left untreated, serious CNS complications and adverse outcomes, including an increased risk of death, can occur.

Algorithms↗
PubMed2006

Dynamics of intraventricular hemorrhage in patients with spontaneous intracerebral hemorrhage: risk factors, clinical impact, and effect of hemostatic therapy with recombinant activated factor VII.

OBJECTIVE: To evaluate predictors of intraventricular hemorrhage (IVH) and IVH growth, impact of IVH growth on outcome, and impact of recombinant activated factor VII (rFVIIa) in patients with intracerebral hemorrhage (ICH). METHODS: We analyzed 374 patients out of 399 who were randomized to rFVIIa (40, 80, or 160 mug/kg) or placebo for ICH (diagnosed within 3 h of symptoms). Risk factors for IVH growth (>2 ml increase in IVH volume at 24 h), and death or severe disability (modified Rankin scale score 4-6) at 3 months were identified (logistic regression). RESULTS: IVH was present in 38% (n = 141) of patients at baseline and 45% (n = 169) by 24 hours. IVH growth, by 24 hours, occurred in 17 and 10% of placebo- and rFVIIa-treated patients, respectively (P = 0.037). Risk factors for IVH growth included baseline mean arterial pressure greater than 120 mmHg, larger baseline ICH volume, IVH present at baseline, shorter time from symptom onset to baseline computed tomographic scan, and treatment (rFVIIa versus placebo) (all, P < or = 0.037). Predictors of death or severe disability included older age, lower baseline Glasgow Coma Score, larger baseline ICH volume, IVH growth greater than 2 ml, IVH present at baseline or 24 hours, and treatment (rFVIIa versus placebo) (all, P < or = 0.0405). CONCLUSION: Presence of IVH at any time and early IVH growth worsen clinical outcome and increase mortality. Elevated mean arterial pressure at baseline may be a modifiable risk factor for IVH growth. Beneficial effects of rFVIIa on ICH outcome may be mediated, at least in part, by reducing IVH growth.

Aging↗
PubMed2006

Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA trial.

BACKGROUND AND PURPOSE: Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven) for preventing early hematoma growth in acute ICH. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 microg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs). RESULTS: Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred. CONCLUSIONS: Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.

Adult↗
PubMed2005

Recombinant activated factor VII for acute intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality. Among patients who undergo computed tomography (CT) within three hours after the onset of intracerebral hemorrhage, one third have an increase in the volume of the hematoma related to subsequent bleeding. We sought to determine whether recombinant activated factor VII (rFVIIa) can reduce hematoma growth after intracerebral hemorrhage. METHODS: We randomly assigned 399 patients with intracerebral hemorrhage diagnosed by CT within three hours after onset to receive placebo (96 patients) or 40 microg of rFVIIa per kilogram of body weight (108 patients), 80 microg per kilogram (92 patients), or 160 microg per kilogram (103 patients) within one hour after the baseline scan. The primary outcome measure was the percent change in the volume of the intracerebral hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Hematoma volume increased more in the placebo group than in the rFVIIa groups. The mean increase was 29 percent in the placebo group, as compared with 16 percent, 14 percent, and 11 percent in the groups given 40 microg, 80 microg, and 160 microg of rFVIIa per kilogram, respectively (P=0.01 for the comparison of the three rFVIIa groups with the placebo group). Growth in the volume of intracerebral hemorrhage was reduced by 3.3 ml, 4.5 ml, and 5.8 ml in the three treatment groups, as compared with that in the placebo group (P=0.01). Sixty-nine percent of placebo-treated patients died or were severely disabled (as defined by a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49 percent, and 54 percent of the patients who were given 40, 80, and 160 microg of rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with the placebo group). Mortality at 90 days was 29 percent for patients who received placebo, as compared with 18 percent in the three rFVIIa groups combined (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral infarction, occurred in 7 percent of rFVIIa-treated patients, as compared with 2 percent of those given placebo (P=0.12). CONCLUSIONS: Treatment with rFVIIa within four hours after the onset of intracerebral hemorrhage limits the growth of the hematoma, reduces mortality, and improves functional outcomes at 90 days, despite a small increase in the frequency of thromboembolic adverse events.

Adult↗
PubMed2005

Treatment of severe coagulopathy after gunshot injury to the head using recombinant activated factor VII.

PURPOSE: Patients with severe penetrating head injury often have a coagulopathy that is difficult to correct. In this report, we describe 3 such patients who were treated with activated factor VII (FVIIa) to stop ongoing hemorrhage that was refractory to conventional treatment. SUBJECTS AND METHODS: We treated 3 patients with severe head injury secondary to gunshot wounds to the head. All 3 patients had ongoing bleeding secondary to a severe consumptive coagulopathy that was refractory to treatment with fresh frozen plasma, platelets, and cryoprecipitate. Recombinant FVIIa was then administered to achieve hemostasis. RESULTS: Administration of FVIIa (90-120 microg/kg) was successful in rapidly achieving hemostasis and correcting abnormal laboratory parameters indicative of coagulopathy in all patients. Although all 3 patients died, control of bleeding made organ donation possible in 2 patients. CONCLUSION: In patients with a severe head injury and coagulopathy, use of FVIIa may help in correction of coagulopathy and decrease transfusion requirements. In patients where ongoing bleeding precludes the declaration of brain death, the use of this agent might help in achieving hemodynamic stability and preserve the possibility of organ donation. The ethical implications of using FVIIa in this situation are discussed.

Adult↗
PubMed2005

To clip or to coil acutely ruptured intracranial aneurysms: update on the debate.

PURPOSE OF REVIEW: The purpose of this review is to consider why the International Subarachnoid Aneurysm Trial (ISAT) led to such an uproar, provide a summary of the criticisms of the study and responses from the investigators, and discuss the implications of ISAT. RECENT FINDINGS: The ISAT was destined for controversy. It pitted two different treatment modalities directly against each other: one a highly evolved, established means for repairing ruptured intracranial aneurysms and the other a radically different, developing approach. The criticisms of the ISAT fall into several categories. They include study site selection, patient selection and the definition of clinical equipoise, relative expertise of the surgeons and interventionists, and the duration and type of follow-up. While some of the criticisms of ISAT reflect unavoidable statistical, design and temporal constraints and thus are of little impact, others are more consequential and revolve around the need for clinical equipoise, and how that was defined across centers. In addition, the question of surgical expertise needs to be addressed. Finally, long-term outcome data are needed. SUMMARY: The study was well designed and executed. The published results met the most up-to-date standards for reporting clinical trials. Important questions remain to be answered, including how to define clinical equipoise and the long-term durability of coiling aneurysms.

Acute Disease↗
PubMed2005

Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage.

INTRODUCTION: Warfarin-associated intracranial hemorrhage (ICH) requires rapid normalization of clotting function. Current therapies are associated with significant complications and/or prolonged time to correction of coagulopathy. Recombinant factor VIIa (FVIIa) might allow faster and safer correction of coagulopathy. METHODS: This article presents a retrospective chart review of all patients with warfarin-associated ICH treated in a neurology/neurosurgery intensive care unit over an 11-month period. RESULTS: All patients were treated to rapidly reverse the warfarin effect. Fifteen patients received vitamin K and fresh frozen plasma (FFP) alone (FFP group). Twelve patients also received FVIIa (FVIIa group). The median times from presentation to an international normalization ratio (INR) of less than 1.3 were 32.2 and 8.8 hours in the FFP the FVIIa groups, respectively (p = 0.016). INR normalized slowly (at 110 and 130 hours, respectively) in two patients with end-stage renal failure who were given FVIIa, one of whom developed disseminated intravascular coagulation after three doses of FVIIa. No other complications occurred from FVIIa administration. One patient in the FFP group developed severe pulmonary edema. CONCLUSION: FVIIa may be an effective adjunct to FFP in warfarin-related ICH, facilitating faster correction of INR and decreasing FFP requirements. A prospective, randomized trial is needed to confirm these preliminary findings and to determine whether there is a clinical benefit.

Aged↗