A Comparison of Hypertonic Saline and Mannitol on Intraoperative Brain Relaxation in Patients with Raised Intracranial Pressure during Supratentorial Tumors Resection: A Randomized Control Trial.

INTRODUCTION: Hyperosmotic agents are used to decrease intracranial pressure (ICP). We aim to compare the effect of euvolemic solutions of 3% hypertonic saline (HTS) and 20% mannitol on intraoperative brain relaxation in patients with clinical or radiological evidence of raised ICP undergoing surgery for supratentorial tumors. MATERIALS AND METHODS: A.prospective double-blind study was conducted on 30 patients randomized into two equal groups. Each patient was administered 5 ml/kg of either 20% mannitol or 3% HTS over 15 minutes (min) after skin incision. Hemodynamic data, brain relaxation and serum electrolyte levels were recorded. RESULTS: Intraoperative brain relaxation was comparable between the two groups. There was a statistically significant difference in the mean arterial pressures (MAPs) between the two groups after one minutes (min) with a greater degree of decrease in blood pressure recorded in the mannitol group (P = 0.041). MAP with mannitol was significantly lower than the preinduction value after 75 min of administration of drug (P = 0.003). Urine output was significantly higher in the mannitol group (P = 0.00). Administration of HTS was associated with a transient increase in serum sodium concentrations, which was statistically significant but returned to normal within 48 h (P < 0.001). CONCLUSIONS: Both mannitol and HTS provided adequate intraoperative brain relaxation. On the contrary, there was no statistically significant fall in blood pressure with HTS. Thus, we advocate the use of HTS over mannitol as it maintains better hemodynamic stability.

Modern Management of Acute Liver Failure.

Acute liver failure is a rare but life-threatening disease that can lead to progressive encephalopathy, intracranial hypertension, and multiorgan failure. In the developed world, the most common cause remains acetaminophen overdose, but there are still many cases in which there is acute liver failure of unknown etiology. The mainstay of acute liver failure management remains supportive care in the critical care setting. If supportive treatment does not stabilize the disease process, the patient may require emergent liver transplantation. This article summarizes the current management of acute liver failure.

Effect of Local Ropivacaine on Hemodynamic Responses in Craniotomy Patients.

BACKGROUND: Increased intracranial pressure (ICP) with hemodynamic is of major concern to anesthesiologists and surgeons in craniotomy surgery. Thus, the management of hemodynamic stability is essential in neuro-anesthesia. This study was performed to investigate the effect of local infiltration of 0.5% ropivacaine on hemodynamic responses in craniotomy patients. MATERIAL AND METHODS: 64 ASA class I -II patients, scheduled for elective craniotomies, were enrolled in this prospective randomized double blind placebo controlled study. These patients were randomly divided into the ropivacaine group, who were administered with 0.5% ropivacaine (n = 32), and the placebo group administered with 0.9% normal saline (NaCl) (n = 32). Anesthesia was induced with 3 µg/kg fentanyl, 5 mg/kg thiopental and 0.5 mg/kg atracurium, and was maintained with isoflurane (0.8-1 = MAC) in 50% N2O, 1 mg/kg /30 minutes, 40% oxygen and 0.05 mg/kg /hour fentanyl. Five minutes prior to surgery, 10 mL of 0.5% ropivacaine was injected in the line of skin incision in the ropivacaine group, while 10 mL of normal saline was injected in placebo group. Thereafter, the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressures (MABP), and heart rate (HR) were measured before infiltration into the incision area, 30 seconds, 3 minutes, 5, 10, and 30 minutes after infiltration into the scalp. For higher BP and HR, an adjunct 0.5 mcg/kg of fentanyl was prescribed and administered. RESULTS: A significant difference was observed for SBP, DBP, MABP and HR, between the two groups at different times during craniotomy (p < 0.05). A significant decrease was observed for SBP, DBP, MABP and HR during craniotomy in 0.5% ropivacaine group as compared with placebo group (p < 0.05). CONCLUSION: Local anesthetic of 0.05% ropivacaine scalp infiltration is effective in clinical usage of regional anesthesia for producing good quality anesthesia, it seems to be a significant choice for management of optimal hemodynamic profile, providing a better hemodynamic stability during craniotomy.

Mercury poisoning as a cause of intracranial hypertension.

Mercury poisoning is a rare but fatal toxicologic emergency. Neurologic manifestations involving the central nervous system are seen usually with chronic mercury intoxication. The most commonly seen complaints are headache, tremor, impaired cognitive skills, weakness, muscle atrophy, and paresthesia. Here, we present a male patient who was chronically exposed to elemental mercury and had papilledema and intracranial hypertension without parenchymal lesion in the central nervous system. A 12-year-old male patient was referred to our emergency room because of severe fatigue, generalized muscle pain and weakness, which was present for a month. Physical examination revealed painful extremities, decreased motor strength and the lack of deep tendon reflexes in lower extremities. He had mixed type polyneuropathy in his electromyography. Whole blood and 24-hour urinary mercury concentrations were high. A chelation therapy with succimer (dimercaptosuccinic acid) was started on the fourth day of his admission. On the seventh day of his admission, he developed headache and nausea, and bilateral papilledema and intracranial hypertension were detected on physical examination. Acetazolamide was started and after 1 month of treatment, the fundi examination was normal. The patient stayed in the hospital for 35 days and was then discharged with acetazolamide, vitamin B6, gabapentin, and followed as an outpatient. His clinical findings were relieving day by day. Although headache is the most common symptom in mercury poisoning, the clinician should evaluate the fundus in terms of intracranial hypertension.

Effect of prolonged therapeutic hypothermia on intracranial pressure, organ function, and hospital outcomes among patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Global cerebral edema (GCE) with subsequent refractory intracranial hypertension complicates some cases of aneurysmal subarachnoid hemorrhage (aSAH), and typically is associated with poorer outcome. Treatment options for refractory intracranial pressure (ICP) cases are limited to decompressive hemicraniectomy (DHC) and targeted temperature management (TTM) with induced hypothermia (32-34 °C). No outcomes comparison between patients treated with either or both forms of refractory ICP therapy exists, and data on the effect of prolonged hypothermia on ICP and organ function among patients with aSAH are limited. METHODS: This is a retrospective study of aSAH patients who underwent DHC and/or prolonged hypothermia (greater than 48 h) for refractory ICP (i.e., ICP >20 mmHg after osmotherapy) in the intensive care unit of a single, tertiary-care academic center. RESULTS: Nineteen individuals with aSAH underwent TTM with or without DHC; sixteen patients underwent DHC alone. The patients in TTM group were younger (median age 44 years) than the DHC without TTM population (median age 60 years). TTM was started on median day 2 with a median duration of 7 days. There were no significant group differences in survival to discharge (59 % vs. 69 %) or in the mean modified Rankin score on follow-up (3.6 vs. 3.7), despite the TTM group having longer hospital length of stay (24 vs. 19 days, p = 0.03), longer duration of mechanical ventilation (20 vs. 9 days, p = 0.04), a higher cumulative fluid balance (12.8 vs. 5.1 L, p = 0.01), and higher APACHEII scores. The median maximal ICP decreased from 23.5 to 21 mmHg within 24 h of hypothermia initiation. There were no significant differences in other markers of end-organ function (respiratory, hematologic, renal, liver, and cardiac), infection rate, or adverse events between groups. CONCLUSIONS: Use of prolonged TTM among aSAH patients with GCE and refractory ICP elevations is associated with a longer duration of mechanical ventilation but is not different in terms of neurological outcomes measured by modified Rankin score or organ function outcomes compared to patients who received DHC alone.

Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

Improvement of hematoma absorption and neurological function in patients with acute intracerebral hemorrhage treated with Xueshuantong.

Spontaneous intracerebral hemorrhage (ICH) leads to high mortality and morbidity. Currently, there is no effective therapy for ICH. Herein we conducted a clinical study in patients with acute ICH to investigate the efficacy of Xueshuantong Injection, a Chinese herbal prescription known for treatment of ischemic diseases in China. Patients (n=63) were randomly assigned to control (n=29) and Xueshuantong Injection treatment (175 mg/d, n=34) groups. Both groups were evaluated using their history and vital signs. The National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume by CT scanning, and inflammatory factors were assessed before and after two weeks treatment. There were no significant differences in all parameters between two groups before treatment. The treatment group showed significant decreases in both NIHSS score and hematoma volume, compared to control group after treatment (P<0.01 and P<0.05, respectively). Furthermore, the inflammatory factors, as measured by leukocytes, neutrophil percentage and C-reactive protein values, were significantly reduced in treatment group compared to control group after treatment (P<0.05, P<0.05, P<0.01 respectively). Our results showed that treatment with Xueshuantong Injection reduced inflammatory response and increased hematoma absorption, which significantly improved recovery of neurological function. This suggests Xueshuantong Injection as a potential treatment of patients with acute ICH.

Modified brainstem auditory evoked responses in patients with non-brainstem compressive cerebral lesions.

The brainstem auditory evoked response (BAER) is sensitive to pontomesencephalic integrity, transtentorial brain herniation, and at times increased intracranial pressure (ICP). The authors report their experience utilizing a recently described rapid rate, binaural, click and 1,000-Hz tone-burst modification of the BAER (MBAER) in 22 symptomatic non-trauma patients with non-brainstem compressive space-taking cerebral lesions. The majority presented with mild to moderate clinical signs suggestive of increased ICP, and focal neurological deficits. The cerebral lesions, mostly tumors (17), averaged 4-5 cm in diameter, with radiological signs of mass effect such as flattening of the sulci, midline shift, and narrowing of the basal cisterns. A number of significant changes in Wave V and V (n) latency and less so amplitude were found in patients compared with age-matched normal volunteers, as well as those again studied after surgical decompression. Similar MBAER changes had been noted in normal volunteers placed in a dependent head position. Possible mechanisms to explain these findings are discussed. The methodology shows promise and if combined with automated peak recognition could make Neuro ICU monitoring practical.

Acute management of acquired brain injury part I: an evidence-based review of non-pharmacological interventions.

PRIMARY OBJECTIVE: To review the literature on non-pharmacological interventions used in acute settings to manage elevated intracranial pressure (ICP) and minimize cerebral damage in patients with acquired brain injury (ABI). MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand-searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations made. RESULTS: Five non-invasive interventions for acute ABI management were assessed: adjusting head posture, body rotation (continuous rotational therapy and prone positioning), hyperventilation, hypothermia and hyperbaric oxygen. Two invasive interventions were also reviewed: cerebrospinal fluid (CSF) drainage and decompressive craniectomy (DC). CONCLUSIONS: There is a paucity of information regarding non-pharmacological acute management of patients with ABI. Strong levels of evidence were found for only four of the seven interventions (decompressive craniectomy, cerebrospinal fluid drainage, hypothermia and hyperbaric oxygen) and only for specific components of their use. Further research into all interventions is warranted.

Decompressive craniectomy for intracerebral hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) has a high mortality rate and leaves most survivors disabled. The dismal outcome is mostly due to the mass effect of hematoma plus edema. Major clinical trials show no benefit from surgical or medical treatment. Decompressive craniectomy has, however, proven beneficial for large ischemic brain infarction with massive swelling. We hypothesized that craniectomy can improve ICH outcome as well. METHODS: We used the model of autologous blood injection into the basal ganglia in rats. After induction of ICH and then magnetic resonance imaging, animals were randomly allocated to groups representing no craniectomy (n = 10) or to craniectomy at 1, 6, or 24 hours. A fifth group without ICH underwent craniectomy only. Neurological and behavioral outcomes were assessed on days 1, 3, and 7 after ICH induction. Furthermore, terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells were counted. RESULTS: After 7 days, compared with the ICH + no craniectomy group, all craniectomy groups had strikingly lower mortality (P < 0.01), much better neurological outcome (P < 0.001), and more favorable behavioral outcome. A trend occurred in the ICH + no craniectomy group toward more robust apoptosis. CONCLUSION: Decompressive craniectomy performed up to 24 hours improved outcome after experimental ICH, with earlier intervention of greater benefit.

Severe traumatic brain injury: maximizing outcomes.

Severe traumatic brain injury is one of the leading causes of death and disability in the United States. The initial management of traumatic brain injury involves early resuscitation, computed tomography scanning, and surgical evacuation of mass lesions, when indicated. Recent research suggests that the prevention and treatment of secondary brain injury decrease mortality and improve outcomes. Specifically, treatment should address not only cerebral protection but also prevention of injury to other organ systems. To achieve the best outcomes, attention must be focused on optimizing blood pressure and brain tissue oxygenation, maintaining adequate cerebral perfusion pressures, and preventing seizures. In addition, maximizing good outcomes depends on proactively addressing the risk of common sequelae of brain injury, including infection, deep venous thrombosis, and inadequate nutrition. Guidelines developed for the management of severe traumatic brain injury have dramatically improved functional neurological outcomes.

Sir Victor Horsley's contributions to the study and treatment of gunshot wounds of the head.

Sir Victor Horsley'S many contributions to neurological surgery include experimental and clinical studies of gunshot wounds (GSW) of the head. Horsley's publications from 1894 to 1897 and 1914 to 1915 on GSWs were reviewed. Horsley described GSWs in animal and clay models, illustrating characteristics of the primary missile tract and secondary cavitation. A transcranial GSW model in 67 dogs related intracranial damage to the projectile's velocity and sectional area, producing a marked sudden increase in intracranial pressure that presumably "tunneled" to the medullary respiratory and cardiac centers. If the resultant sudden apnea was treated with artificial respiration and prompt surgical decompression, the animal often survived. In these animal experiments, Horsley clearly described increased intracranial pressure, hypertension, and bradycardia-later recognized as the Cushing response or triad. With the onset of World War I, Horsley again reviewed the ballistics of military weaponry, emphasizing projectile spin and velocity as the main wounding mechanisms. He was outspoken against the "wicked tradition" of neglecting cranial GSWs and personally treated cases with aggressive respiratory support and prompt decompression of devitalized tissue. Horsley's contributions to the experimental and clinical aspects of GSWs to the head are consistent with his other important contributions to neurosurgery and have largely stood the test of time.

L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke.

Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.

Hyperbaric oxygen improves survival in heatstroke rats by reducing multiorgan dysfunction and brain oxidative stress.

Hyperbaric oxygen has been found to be beneficial in treating heatstroke animals. We attempted to further assess the possible mechanism of therapeutic protection offered by hyperbaric oxygen in experimental heatstroke. Anesthetized rats, immediately after the onset of heatstroke, were randomized into the following groups and given: a) hyperbaric oxygen (100% O(2) at 253 kPa for 1 h); or b) normal air. They were exposed to 43 degrees C temperature to induce heatstroke. When the untreated rats underwent heat stress, their survival time values were found to be 20-24 min. Resuscitation with hyperbaric oxygen increased the survival time to new values of 152-176 min. All untreated heatstroke rats displayed cerebrovascular dysfunction (evidenced by hypotension, intracranial hypertension, and cerebral hypoperfusion, hypoxia, and ischemia), hypercoagulable state (evidenced by increased levels of activated partial thromboplastin time, prothrombin time, and D-dimer, but decreased values of platelet count and protein C in plasma), and tissue ischemia/injury (evidenced by increased levels of creatinine, serum urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in plasma, and dihydrobenzoic acid, lipid peroxidation, and oxidized-form glutathione/reduced-form of glutathione ratio in hypothalamus). The cerebrovascular dysfunctions, hypercoagulable state, tissue ischemia/injury, and brain oxidative stress that occurred during heatstroke were all suppressed by hyperbaric oxygen therapy. The current results indicate that hyperbaric oxygen therapy may resuscitate rats that had a heatstroke by decreasing multiple organ dysfunction and brain oxidative stress.

The flavonoid baicalin protects against cerebrovascular dysfunction and brain inflammation in experimental heatstroke.

The present study was performed to assess the prophylactic effect of baicalin, a flavonoid compound, in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1mL per kg body weight) or baicalin (10-40mg per kg body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 20-28min. Pretreatment with intravenous doses of baicalin significantly improved survival during heatstroke (65-248min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, and dihydroxybenzoic acid (DHBA) in hypothalamus. In addition, both serum and hypothalamic levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well as plasma levels of creatinine, serum urea nitrogen, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase were elevated after heatstroke onset. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of baicalin before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, and the increased levels of NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and DHBA in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in both the serum and hypothalamus, and renal and hepatic dysfunction were suppressed by baicalin pretreatment. In contrast, both the serum and hypothalamic levels of IL-10 were significantly elevated by baicalin during heatstroke. We successfully demonstrated that baicalin can be used as a prophylactic agent for heatstroke. In particular, baicalin may protect against cerebrovascular dysfunction and brain inflammation in heatstroke.

Intracranial pressure response to induced hypertension: role of dynamic pressure autoregulation.

OBJECTIVE: Induced hypertension is commonly used to improve cerebral perfusion, but this treatment may have the deleterious side effect of raising intracranial pressure (ICP). We tested the hypothesis that dynamic pressure autoregulation testing could identify patients who might develop increased ICP during induced hypertension. METHODS: Twenty-two studies were performed in 21 patients. Baseline dynamic testing of autoregulation by cuff deflation and carotid compression techniques was performed. After phenylephrine was infused to increase mean arterial pressure by 20 to 30 mm Hg, cuff deflation tests were repeated. RESULTS: The average increase in mean arterial pressure was 32.2 +/- 16.1 mm Hg. This increase was accompanied by increased flow velocity (P < 0.001), brain tissue PO2 (P = 0.011), and regional cerebral blood flow (P = 0.008). Also, dynamic pressure autoregulation consistently improved (P = 0.015). Induced hypertension caused increased ICP (iICP) in 12 patients and a decrease in ICP (dICP) in 9. Baseline jugular venous oxygen saturation in the iICP group was 82 +/- 10% compared with 70 +/- 10% in dICP patients (P = 0.02). Baseline dynamic autoregulatory index for the cuff deflation tests (1.8 +/- 1.4) and baseline transient hyperemic response ratio for the carotid compression tests (1.11 +/- 0.07) were significantly lower in iICP patients (dICP group: autoregulatory index 3.2 +/- 1.7, P = 0.06; transient hyperemic response ratio 1.26 +/- 0.11, P = 0.009). Flow velocity increased more with the increase in blood pressure in the iICP group than in the dICP group: 19.0 +/- 6.8 cm/s versus 10.2 +/- 6.3 cm/s (P = 0.007). CONCLUSION: The patients who had an increase in ICP with induced hypertension had a greater degree of impairment of autoregulation and induced hypertension resulted in a greater increase in flow velocity.