George Mychaskiw

The Bispectral Index (BIS) has become widely accepted as a measurement of hypnosis under anesthesia. It is derived from a processed electroencephalogram and computer algorithm that assigns a numerical value based on the probability of consciousness. Values <60 correlate with a low probability of consciousness (1). We report a case wherein a patient experienced explicit recall of intraoperative events, despite a BIS of 47. Case Report A 28-yr-old, 85-kg male with a history of smoking, hypercholesterolemia, and hypertension presented to the operating room for three coronary artery bypass grafts, secondary to severe coronary artery disease with normal left ventricular function. There was no family history significant for heart disease. The patient was employed as a corrections officer and had no previous medical training or experience with cardiac surgery. He had no history of recreational drug use or alcohol abuse. His surgical history was previously negative. Monitors applied included an Aspect A-2000 BIS monitor (Aspect Medical Systems, Newton, MA). Anesthesia was induced with thiopental, 4 mg/kg, nitrous oxide, 70%, in oxygen and sevoflurane, 2–3%, with paralysis induced by vecuronium. After endotracheal intubation, he was turned laterally, and preservative-free morphine, 5 μg/kg, administered via a 22-gauge spinal needle at the L3-4 interspace. The patient was then returned to a supine position for the duration of surgery. During placement of the intrathecal morphine, the BIS sensor had become dislodged and was replaced after returning to the supine position. As the monitor was turned on, electrode impedances were automatically checked and within acceptable limits. Anesthesia was maintained with sevoflurane and nitrous oxide until the start of cardiopulmonary bypass (CPB), when it was changed to isoflurane in oxygen. At the conclusion of the case, the neuromuscular block from vecuronium was reversed, and the patient was awakened, tracheally extubated, and transferred to the cardiovascular intensive care unit in stable condition. He had an uneventful recovery and was discharged home on the fourth postoperative day. During his postanesthesia interview, 48 h after surgery, the patient reported that he could recall voices in the operating room, the sound of the sternal saw being tested, and could feel his chest being opened. The patient denied any pain, and did not recall anything after sternotomy. He clearly described the sound of the nitrogen-powered sternal saw to the anesthesiology resident conducting the postoperative evaluation. This was elicited spontaneously by the patient and not as a result of a specific inquiry about recall. The patient had no prior history of intraoperative recall. Review of the medical record revealed a BIS of 47 at the time of sternotomy, 35 min after induction of anesthesia. At the time of sternotomy, Fio2 was 0.26, Fin2o was 0.67, and inspired sevoflurane was 2%. The sevoflurane initially was started at 4%, and had been at 3% for most of the time before sternotomy. The patient’s heart rate and blood pressure were slowly decreasing after the induction, and the sevoflurane concentration was also slowly decreased to 2%, as noted. The vaporizer in use on the anesthesia machine had previously functioned well, and end-tidal sevoflurane was appropriately detected by a RASCAL gas-monitoring device (Ohmeda, Tewksbury, MA). Despite this, the patient was quite satisfied with his anesthetic and reported no psychological difficulties resulting from the awareness event. Discussion Awareness during anesthesia is a significant complication with potentially devastating psychological consequences. Up to 70% of patients who suffer intraoperative awareness may experience after-effects, similar to a postraumatic stress disorder (2). This has become a particularly infamous and emotional issue during the last decade, as several cases became publicized through television and radio talk shows. Awareness during cardiac surgery has been reported in as many as 23% of patients (3). Most cases occur during or after rewarming from CPB and are attributed to alterations in drug pharmacokinetics and dynamics resulting from the bypass process. Other cases are associated with painful procedures such as sternotomy and intubation (4). This case is particularly unusual, as the patient had not yet undergone sternotomy and was stable with only a minimal level of surgical stimulation. Additionally, the patient’s anesthetic essentially consisted of nitrous oxide and volatile anesthetic at a total concentration of more than 1 MAC, which had been maintained for at least 30 minutes before the recall occurred. Volatile anesthetics are especially protective of intraoperative awareness and have a well-documented amnestic property at concentrations <1 MAC (5). The patient in this case was administered an anesthetic that we frequently use if early or immediate postoperative extubation is desired. No previous instances of recall have been discovered in any other patient using the same anesthetic either before or since (approximately 40 patients), although this small sample size lacks the statistical power to draw conclusions about a relatively uncommon event. Indeed, most patients are significantly sedated on emergence, despite the avoidance of systemic narcotics or benzodiazepines. Although the etiology for this sedation is unclear, we speculate that it may be related to cerebral changes secondary to CPB. The first several patients who received this anesthetic had intrathecal morphine administered at a dose of 10 μg/kg. This was decreased to 5 μg/kg as a result of excessive sedation associated with the larger dose. It should be noted that this is the youngest patient in our series and it is unclear if his age may have influenced the propensity for awareness. Because of our avoidance of any additional narcotics or benzodiazepines, we depended heavily on the BIS as a monitor of adequate hypnosis. The BIS frequently increases during rewarming from CPB and isoflurane is administered via the oxygenator for much of the pump run. The monitor has performed well under the conditions encountered during cardiac surgery and the BIS usually trends as expected, increasing to more than 95 as the patients are awakened and tracheally extubated at the conclusion of the case. Although cardiac surgery and, specifically, CPB cause alterations in cerebral blood flow, the resultant electroencephalographic changes should be accurately interpreted by the BIS, but this has not been studied. In conclusion, we report a case of explicit recall at a BIS of 47 in a patient during cardiac surgery using a significant dose of volatile anesthesia. Consciousness and memory formation during anesthesia are not completely understood phenomena. It is apparent that there may be an incidence of intraoperative awareness that persists despite the best preventative efforts. Additionally, although the BIS is a valuable tool in the monitoring of hypnosis, it is a probability function, and it can be expected that recall may occur despite a relatively low displayed value. Although the chance of recall at a BIS of <60 may be small, it is obviously not guaranteed, consistent with a statistical outlier in a population. Given a sufficiently large number of cases, this phenomenon is not unexpected. Fortunately, our patient suffered no adverse sequelae. In the preanesthetic evaluation, it is our practice to discuss the possibility of recall with all patients, and again discuss any possible awareness during the postanesthesia follow-up. It is unknown whether these discussions may alleviate the psychological impact of intraoperative awareness.

Cerebral vascular diseases, such as neonatal encephalopathy and focal or global cerebral ischemia, all result in reduction of blood flow to the affected regions, and cause hypoxia-ischemia, disorder of energy metabolism, activation of pathogenic cascades, and eventual cell death. Due to a narrow therapeutic window for neuroprotection, few effective therapies are available, and prognosis for patients with these neurological injuries remains poor. Hyperbaric oxygen (HBO) has been used as a primary or adjunctive therapy over the last 50 years with controversial results, both in experimental and clinical studies. In addition, the mechanisms of HBO on neuroprotection remain elusive. Early applications of HBO within a therapeutic window of 3-6h or delayed but repeated administration of HBO can either salvage injured neuronal tissues or promote neurobehavioral functional recovery. This review explores the discrepancies between experimental and clinical observations of HBO, focusing on its therapeutic window in brain injuries, and discusses the potential mechanisms of HBO neuroprotection.

Radiofrequency energy has historically been used for electrocautery in surgery and as ablative therapy of conduction pathways in conditions such as Wolff-Parkinson-White syndrome and refractory supraventricular tachycardia. Recently, the clinical uses of radiofrequency ablation have been expanded to include treatment of both hepatic and pulmonary neoplasms (1). We describe the anesthetic management of a patient who experienced intraoperative pulmonary hemorrhage while undergoing radiofrequency ablation of a primary lung tumor. Case Report A 70-yr-old man presented for radiofrequency ablation of an adenocarcinoma of the right lung measuring 2.5 × 3.5 cm. He had a history of bilateral lung lesions and had undergone several courses of chemotherapy (Taxol and Carboplatin), as well as one surgical wedge resection. His medical history was significant for hypertension, atherosclerotic heart disease, and benign prostatic hypotrophy. His medications included aspirin 81 mg/d, which was discontinued 1 wk before admission, fluvastatin 20 mg/d, enalapril 20 mg/d, clopidogrel 75 mg/d, oxycodone controlled release tablets 10 mg every 12 h, and tamsulosin 0.4 mg/d. At the time of admission, the patient related a history of easy bruising. Physical examination was unremarkable. Chest radiogram was significant for a midleft lung mass and an upper right lung mass. Laboratory findings included a hematocrit of 45%, platelet count of 289,000, a partial thromboplastin time of 33.2 s, and a prothrombin time of 11.7 s. No studies of platelet function were performed. On the day of the procedure, the patient underwent an uneventful induction of anesthesia with sodium thiopental 4 mg/kg, fentanyl 1.8 μg/kg, and vecuronium 0.1 mg/kg. His trachea was intubated with an 8.0-mm endotracheal tube without difficulty. Anesthesia was maintained with desflurane 3%–4%, 100% oxygen, and 50 μg of fentanyl boluses. The patient remained stable during positioning and initial computed tomography (CT) scanning. Approximately 2 h after the radiofrequency ablation began, the patient suddenly had a decrease in arterial oxygen saturation to 84% followed by hypotension with a decrease of systolic blood pressure to 79 mm Hg. The blood pressure was restored to 150 mm Hg with 2 boluses of phenylephrine, 100 μg each, and a 400-mL bolus of lactated Ringer’s solution, positive end-expiratory pressure of 10 cm, was applied and ventilation controlled. Despite these measurements, it took 5 min to restore the arterial oxygen saturation to 97%. A CT scan performed at the anesthesiologist’s suggestion revealed extensive hemorrhage into the right lung and right pleural cavity (Fig. 1). The patient was transferred from the CT scanner to angiography so that emergency pulmonary and bronchial arteriograms could be performed. The right internal jugular vein was cannulated, and a blood sample was sent for type and cross-match. A fiberoptic examination through the existing endotracheal tube revealed blood at the carina, and a 39F double lumen endobronchial tube was placed to isolate the lungs.Figure 1: Computed tomography (CT) scan demonstrating massive hemorrhage into the right lung and pleural cavity. Note the appearance of air in bronchi (arrow) surrounded by intraparenchymal blood.The hemorrhage was both intraparenchymal and extrapleural, but the pulmonary and bronchial arteriograms failed to identify a distinct source of bleeding. After completion of the arteriograms, the patient was transferred to the intensive care unit. The patient remained intubated and mechanically ventilated for several days after surgery because of difficulties with oxygenation. During the first postoperative day, his hematocrit decreased from a preoperative value of 45% to 31%. Platelets were not transfused, and the patient had no further hemorrhage. On postoperative Day 8, while still intubated, the patient had a non-Q wave myocardial infarction. He was finally extubated on postoperative Day 11. Eight days later, he suffered an episode of pulmonary aspiration, which eventually led to his death on postoperative Day 23. Discussion Radiofrequency ablation is the use of radiofrequency energy to thermally destroy living tissue. Today, its use has been expanded to include bulk tissue ablation of hepatic and pulmonary neoplasms (1). Because many of these neoplasms are not amenable to curative surgical resection, radiofrequency ablation represents an important new addition to the treatment armamentarium. The energy for radiofrequency ablation is produced by a generator and is introduced into the tumor through a probe placed under CT or ultrasound guidance. The energy emerges at the tip of the probe via an array of tines and is introduced as alternating current. Ions present in tissue molecules oscillate in response to the alternating current because of their polarity. This ionic oscillation results in frictional heat, which leads to coagulation necrosis and protein/enzyme dysfunction. The position of the probe is repeatedly changed until the entire bulk of the tumor has been heated. At each probe location, the power of the energy administered is increased by increments until a critical temperature sufficient to cause tissue destruction is reached (80°C). The presence of a pacemaker is an absolute contraindication. The presence of metallic implants is a relative contraindication, depending on their proximity to the procedure site. This case involved radiofrequency ablation of a lung tumor and demonstrated one of the known complications of the procedure, which is hemorrhage. Other complications of radiofrequency ablation of pulmonary lesions include pneumothorax (20% incidence), infection (<1%), and bronchopleural fistula formation (<1%) (Sewell P., Department of Radiology, University of Mississippi School of Medicine, personal communication, November 2001). Hemorrhage occurs infrequently (<1%), is usually mild, and is of little clinical significance. However, the patient in this case was taking clopidogrel, a potent platelet inhibitor. Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor, thereby inhibiting platelet aggregation. It irreversibly modifies the platelet ADP receptor. Consequently, platelets exposed to clopidogrel are affected for the remainder of their life span. Inhibition of platelet aggregation can be seen two hours after a single oral dose (Manufacturer’s Package Insert, Sanofi-Synthelabo Inc, New York). At steady state, the average inhibition level is between 40% and 60%. After treatment is discontinued, platelet aggregation gradually returns to baseline values usually in about five days. The package insert states that if a patient is to undergo elective surgery, and an antiplatelet effect is not desired, clopidogrel should be discontinued seven days before surgery. In urgent or emergent situations, platelet transfusion can ameliorate clopidogrel’s antiplatelet effects. The amount of platelets transfused to achieve adequate hemostasis is variable and can be guided by platelet function testing. In retrospect, given the elective nature of the case, we should have postponed the procedure and discontinued the clopidogrel until platelet function normalized. Considering the infrequency of hemorrhage as a complication and its generally limited nature, many surgeons would elect to proceed, regardless. However, the clinical experience with patients on clopidogrel undergoing radiofrequency ablation is very limited because the procedure itself is new and relatively uncommon, used in only a few centers nationwide. Thus, it seems prudent to discontinue clopidogrel for about a week and evaluate platelet function before proceeding with radiofrequency ablation therapy. Historically, bleeding time has been measured in patients with platelet dysfunction in an attempt to predict the possibility of surgical bleeding. However, bleeding time has not proven to be a consistently reliable predictor (2). A new device, the PFA-100 (Sysmex UK Ltd, Buckinghamshire, Great Britain), is now available to assist in the evaluation of platelet function. The PFA-100 is designed to measure platelet-related primary hemostasis. It is able to detect qualitative platelet defects, including drug-induced platelet dysfunction. The instrument uses two disposable cartridges: a collagen/epinephrine and a collagen/ADP cartridge. Citrated whole blood is aspirated through a capillary into an aperture, the surface of which is coated with collagen to which ADP or epinephrine is added. Platelets adhere, undergo a release reaction, aggregate, and occlude the aperture by a primary hemostatic plug. The closure time that is required for blood to occlude the aperture is measured. The differences in the closure times for the two cartridges allows for differentiation to be made among congenital thrombocytopathy, von Willebrand disease, and drug-induced platelet dysfunction. The sensitivity and specificity of the PFA-100 are 94.9% and 88.8%, respectively (3). These values compare favorably with the sensitivity and specificity of the more labor-intensive platelet aggregometry (94.3% and 88.3%, respectively) (3). In addition, results can be obtained with the PFA-100 in 30 minutes rather than the 3 hours required for platelet aggregometry. This test is especially sensitive and useful in the evaluation of pharmacological derangement of platelet function seen with clopidogrel. The computerized Thrombelastograph coagulation analyzer (TEG®; Haemoscope Co, Skokie, IL) is used in some institutions. It detects and records the kinetic changes in a sample of whole blood as the clot forms, retracts, or lyses. The resultant coagulation profile is therefore a measure of clot kinetics (formation and dissolution) and of clot quality (the ability to perform the work of hemostasis). The TEG® coagulation analyzer is a global test of hemostatic dysfunction and is not a specific test for platelet dysfunction (4–6). Although it can detect platelet dysfunction after antiplatelet drug therapy, the TEG® coagulation analyzer is less sensitive than the PFA-100 for this purpose. Radiofrequency ablation is a new approach to the treatment of pulmonary neoplasms. Although the incidence of complications is small, the presentation may be dramatic, as in this case. We would recommend that patients undergoing this procedure have a large-bore IV cannula, an arterial cannula, and a current type/screen. In addition, there should be heightened awareness of any potential for coagulopathy. Most of these patients have received chemotherapy with possible bone marrow suppression and thrombocytopenia. In addition, many of these patients are elderly or are chronic tobacco users with an increased incidence of peripheral vascular disease. A careful medication history should be taken to determine whether any medications have been prescribed that might adversely affect hemostasis, and an appropriate preoperative evaluation should be performed. Finally, as pneumothorax is the most prevalent complication of the procedure, personnel involved in these cases should be vigilant for the occurrence of pneumothorax and prepared to treat it if required.