Ahmed E. Badr

Down regulation of COX-2 is involved in hyperbaric oxygen treatment in a rat transient focal cerebral ischemia model.

The effect of hyperbaric oxygen (HBO) on cyclooxygenase-2 (COX-2) expression after transient focal ischemia was evaluated. A rat middle cerebral artery occlusion/reperfusion (MCAO) model was produced using the intraluminal filament method. After 2 h of occlusion, 24 h of reperfusion, brains were removed. Three atmospheres absolute HBO for 1 h was administered at 6 h after reperfusion. The infarct volume was evaluated by 2,3,7-triphenyltetrazolium chloride staining. COX-2 mRNA expression was measured by reverse transcription polymerase chain reaction, and COX-2 protein expression was analyzed by Western blot. The results showed that HBO applied at 6 h after reperfusion significantly reduces infarct area as compared with no-treatment group. HBO decreased COX-2 mRNA and protein levels, which were upregulated after ischemia/reperfusion. HBO had no direct effect on COX-2 protein expression in matched normal rats. We conclude that (1) early intervention with HBO within 6 h reduces infarction. (2) The neuroprotective effect of HBO might lead to an inhibition of COX-2 over-expression in cerebral cortex.

Hyperbaric oxygenation prevented brain injury induced by hypoxia-ischemia in a neonatal rat model.

The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of an individual leads to the damaging of immature neurons resulting in behavioral and psychological dysfunctions, such as motor or learning disabilities, cerebral palsy, epilepsy or even death. No effective treatment is currently available and this study is the first to use hyperbaric oxygen (HBO) as a treatment for neonatal HI. Herein, we sought out to determine if HBO is able to offer neuroprotectivity against an HI insult. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O(2) at 37 degrees C). HBO treatment was administered by placing pups in a chamber (3 ATA for 1 h) 1 h after hypoxia exposure. Brain injury was assessed based on ipsilateral hemispheric weight divided by contralateral hemispheric weight, light microscopy, and EM. Sensorimotor functional tests were administered at 5 weeks after hypoxia exposure. After HI, the ipsilateral hemisphere was 52.65 and 57.64% (P<0.001) of the contralateral hemisphere at 2 and 6 weeks, respectively. In HBO treated groups, the ipsilateral hemisphere was 77.77 and 84.19% (P<0.001) at 2 and 6 weeks. There was much less atrophy and apoptosis in HBO treated animals under light or electron microscopy. Sensorimotor function was also improved by HBO at 5 weeks after hypoxia exposure (Chi-square, P<0.050). The results suggest that HBO is able to attenuate the effects of HI on the neonatal brain by reducing the progression of neuronal injury and increasing sensorimotor function.

Effect of hyperbaric oxygen on striatal metabolites: a microdialysis study in awake freely moving rats after MCA occlusion

We have shown that hyperbaric oxygen (HBO) reduced cerebral infarction in rat middle cerebral artery occlusion model (MCAO). The present study was undertaken to evaluate the effect of HBO on ischemic striatal metabolites at different times after MCAO and reperfusion. A rat MCAO model was produced via the intraluminal filament method. After 2 h of occlusion the suture was removed and reperfusion was allowed. The rats were sacrificed at 24 h after reperfusion. HBO treatment was administered by putting rats in the HBO chamber at 3 atmospheres absolute (ATA) HBO for 1 h. Glucose, lactate, pyruvate, and glutamate in striatal extracellular fluid were collected and measured by a microdialysis system at 7, 10, and 24 h after reperfusion. Glucose, pyruvate and glutamate concentrations were increased after reperfusion. HBO treatment decreased glucose, pyruvate, and glutamate almost to the control level (preocclusion level). The lactate concentration remained unchanged after ischemic/reperfusion and after HBO treatment. This study suggested that altered brain energy metabolites and excitatory amino acids occurred during cerebral ischemia and and HBO regulated these striatal metabolites, which might contribute to the protective effect of HBO in cerebral ischemia.

Optison (FS069) disrupts the blood-brain barrier in rats.

Optison is a new echocardiographic contrast agent, designed for IV injection, that is very useful in delineating cardiac structures during ultrasound examination. Because Optison could be a valuable adjunct in the diagnosis and evaluation of congenital heart disease, this study was undertaken to assess its effects on the blood-brain barrier when introduced directly in the cerebral circulation, as might occur with some congenital lesions. In this study, Sprague-Dawley rats were anesthetized, and Optison, at various dosages, was injected into the carotid artery. After this, Evans blue dye, a marker for blood-brain barrier disruption, was injected at different time intervals. Gross and histologic examination of the animals’ brains revealed disruption of the blood-brain barrier that appeared to be Optison-dosage-dependent. Although the mechanism for this disruption is unclear, it may be related to the use of octofluoropropane gas used in the Optison as a contrast medium. Further studies are necessary to determine the pathologic consequences of Optison’s effects on the blood-brain barrier. Implications Optison appears to disrupt the blood-brain barrier when introduced directly into the cerebral arterial circulation. This may be related to the octafluoropropane gas used in Optison as a contrast medium. Optison should be used with caution when the possibility of a right-to-left shunt exists.

Metabolic acidosis associated with a New formulation of Propofol

PROPOFOL is used for the intravenous induction of anesthesia and for sedation in the intensive care unit. Two formulations of propofol are available in the United States: Diprivan brand (Zeneca Pharmaceuticals, Wilmington, DE) and Propofol (Baxter Pharmaceutical Products, Inc., New Providence, NJ). The formulary of the University of Mississippi School of Medicine recently changed from the Zeneca product to the Baxter product for economic reasons. We report a case of severe metabolic acidosis associated with the new product.

Comparison of awake endotracheal intubation in patients with cervical spine disease: the lighted intubating stylet versus the fiberoptic bronchoscope.

A wake endotracheal intubation followed by brief neurological examination before the induction of general anesthesia is an accepted practice for patients with cervical spine disease with symptoms of myelopathy and for patients at risk of spinal cord compression during standard endotracheal intubation (1). Awake intubation is performed with the fiberoptic bronchoscope (FOB) either by the nasal or oral route, the nasal route being relatively more common. The success rate of FOB intubation ranges from 72% to 98% (2-5). The lighted intubating stylet (LIS) has been used for indirect endotracheal intubation with success rates between 88% and 100% (6-9). Studies have demonstrated the efficiency of the LIS for managing the difficult airway in children (10) and in patients with maxillofacial injury (11). Use of the LIS is part of the ASA’s difficult airway algorithm (12). Because the LIS allows endotracheal intubation with minimal movement of the cervical spine, it is ideally suited for patients with myelopathy. Fox et al. (13) compared the LIS with blind nasotracheal intubation in awake patients with cervical spine disease and found the LIS to be superior, with greater speed, fewer required attempts, and reduced incidence of complications. Because awake nasotracheal intubation with the FOB is a common method of endotracheal intubation in patients with myelopathy, it is important to compare this technique with orotracheal intubation using the LIS.

Metabolic alterations in cerebrospinal fluid from double hemorrhage model of dogs

Abstract Even though cerebral vasospasm after subarachnoid hemorrhage (SAH) causes cerebral ischemia or infarction, the metabolic alterations in cerebrospinal fluids (CSF) after SAH have not been studied. This study was undertaken to measure the levels of glucose, lactate, pyruvate and glutamate in CSF from double hemorrhage dog models. Thirty-two mongrel dogs of either sex, weighing 18-24 kg, underwent double hemorrhage by percutaneous needle puncture of the cisterna magna and injection of autologous blood on day 0 and day 2. The dogs were then sacrificed on day 3, 5 and 7, after collecting CSF. In another study, the dogs were treated with mitogen-activated protein kinase (MAPK) inhibitors PD98059 and U0126, and caspase-2 and caspase-3 inhibitors from day 3 to day 6 after initial blood injection. CSF was collected on day 7 before dogs were sacrificed. The concentration of glucose, lactate, pyruvate and glutamate in CSF was measured by photometrical method. Compared with CSF collected on day 0, glucose was decreased on days 5-7, lactate was increased on days 2-7, pyruvate was increased on days 2-7, and glutamate was increased on days 3-7 (p < 0.05). In the groups treated with MAPK or caspase inhibitors, most of the metabolic alterations remained unchanged as compared with CSF from untreated dogs. Clinically, caspase inhibitors-2 and-3, and MAPK inhibitor U0126 all failed to prevent vasospasm. MAPK inhibitor PD98059 partially prevented vasospasm. Our data demonstrated a metabolic alteration of glucose, glutamate, lactate and pyruvate in CSF during cerebral vasospasm. This metabolic change is consistent with the time course of cerebral vasospasm. This study suggests that brain energy metabolites and excitative amino acids are altered during cerebral vasospasm. [Neurol Res 2001; 23: 87-92]

Case Series or Uncontrolled Clinical Study

To the Editor:—We read with interest the article by Ramsay and Luterman and accompanying editorial discussing the use of high-dose dexmedetomidine as a single-agent intravenous anesthetic. We have several concerns, both with the technique described and the journal’s editorial position. As to the case series itself, we wonder what was the basis for the clinical choice to use doses of dexmedetomidine at more than 7 to 50 times the recommended dose range of 0.2–0.7 g·kg ·h 1 as the sole anesthetic. Ebert et al.’s work with volunteers was extremely limited and in no way established dexmedetomidine as a safe single-agent anesthetic. Indeed, doses of dexmedetomidine lower than those in the case series have been recently reported as “accidental overdose” and are accompanied by guidelines for the management of same. Although Ramsay and Luterman’s cases imply that the doses were increased when the patients could not tolerate the procedures at lower dose levels, there is no mention of the initial anesthetic plan. Did the authors undertake the anesthetics with the expectation of using dexmedetomidine at massive, unstudied doses? Given the properties of dexmedetomidine at its usual clinical dose range, it is unlikely that patients would be able to tolerate the procedures described without either supplementation or rapid escalation to massive doses, as actually occurred. We find no convincing evidence in the literature to believe that their course of action could be chosen with confidence in its safety and efficacy. The intraoperative management of the cases is also unusual. We fail to understand their need to avoid the use of supplemental oxygen except when absolutely necessary. The argument regarding electrocautery is unconvincing. It is almost as if the decreased margin of safety is used as a demonstration of dexmedetomidine’s properties with respect to maintenance of ventilation. In the two cases that did not receive supplemental oxygen, were the patients subsequently placed on oxygen in the postanesthesia care unit? Finally, we question the assertion that recovery time in these patients was not significantly prolonged when compared with many conventional anesthetic techniques. A recovery time and postanesthesia care unit stay of 2 to 3 h is considered by many to be significantly prolonged and is not a desirable side effect. We are therefore concerned that ANESTHESIOLOGY tacitly endorses this anesthetic technique by calling it “another arrow for the clinician’s quiver” in the accompanying editorial. On the basis of Ebert et al.’s two volunteers and the three cases described by Ramsay and Luterman, are we to assume that this is now an acceptable practice? Certainly, we all daily administer many medications “off-label” in a safe and reasonable manner. There comes a point, however, when the off-label use of a drug crosses the line of “reasonable” and becomes a deviation from the standard of care. Until properly controlled, Institutional Review Board reviewed clinical studies (with appropriate informed patient consent) are conducted addressing safety and efficacy issues of the doses in question, it is premature to call single-agent intravenous dexmedetomidine “another arrow for the clinician’s quiver.” A case report or small series of cases should highlight an unusual occurrence, pathology, or unanticipated anesthetic intervention, rather than act as a proving ground for new anesthetic techniques. There is nothing in the article to suggest that the patients involved provided informed consent as to the unusual nature of the anesthetic. Similarly, it does not appear that an Institutional Review Board or hospital ethics committee was consulted regarding this “case series.” The practice of anesthesiology is neither a contest of skills nor a game of what one can get away with. The essence of the practice of anesthesiology is the planning and administration of the safest and most efficient anesthetic for a given individual patient using principles grounded in science and controlled clinical studies. An unusual technique that worked in three patients does not rise to this standard and sidesteps the checks and balances of ethical scientific investigation. Finally, the lack of complete disclosure of conflicts of interest on Dr. Ebert’s part is disturbing. The attestation states, “Dr. Ebert is not supported by, nor maintains any financial interest in, any commercial activity that may be associated with the topic of this editorial.” This may be true only in the strictest and most limited interpretation of the statement, but ignores Dr. Ebert’s long and close association with Abbott Laboratories (Abbott Park, IL) and previous substantial financial support and honoraria. In fact, the study cited by Ebert in the editorial, examining high-dose dexmedetomidine in volunteers, was itself supported by a grant from Abbott Laboratories. At best, this is disingenuous. The casual reader of the journal should be fully aware that an unproven anesthetic technique, utilizing an expensive drug manufactured by Hospira, Inc. (Lake Forest, IL), a wholly-owned spin-off company of Abbott Laboratories, is advocated by an Abbott-funded investigator and is trumpeted by editorial writers with a long history of close association and support from Abbott Laboratories. It is difficult to understand how one can consider this an objective review of scientific data.