ANESTH ANALG 1992;75461-71
investigation will be necessary to refine our understanding of the effects of EAA that we have reported in our study. Kenneth J. Tuman, MD Robert J. McCarthy, PharmD Anthony D. Ivankovich, MD Department of Anesthesiology Rush-Presbyterian-St. Luke's Medical Center Chicago, It 60622
References 1. Tuman KJ, McCarthy RJ, March RJ, DeLaria GA, Pate1 RV, Ivankovich AD. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 1991;73:696-704. 2. Christopherson R, Frank SM, Norris EJ, et al. Reoperation after lower extremity vascular surgery is more common after general than epidural anesthesia (abstract). Proceedings of the Society of Cardiovascular Anesthesia Annual Meeting, Boston, May 3, 1992.
Differential Awakening To the Editor: I would like to propose a new phenomenologic term, "differential awakening," for the clinical anesthesiologist. Over the years as a practicing neuroanesthesiologist, I and others have observed that patients with cerebral ischemia or mass lesions frequently show evolving lateralizing neurologic signs on awakening. Immediately on awakening, unilateral return of motor function is frequently delayed but improves, and returns to complete function over about 10-30 min, thus, the term "differential awakening." This process is clinically significant because it is clearly different from a surgical neurologic deficit that is expected to return slowly. It is also different from immediate surgical complications that might require reopening of the cranium or a computed axial tomographic scan for further diagnosis. Three theories could explain the phenomenon of differential awakening. First, anesthetics enter the brain and are trapped in areas that are injured by ischemia or trauma, and at the end of anesthesia, these anesthetics escape more slowly from the injured areas. Second, perhaps the areas of cerebral injury are more sensitive to low concentrations of the anesthetic, resulting in a slower unilateral emergence. Last, in patients who suffer destructive neurologic damage with full recovery, it is believed that secondary pathways compensate and accomplish the function of the destroyed neurons; perhaps these secondary pathways are only functional in a completely awake state. Roy F. Cucchiara, MD Department of Anesthesiology University of Florida College of Medicine Box 100254 Gainesville, FL 32620-0254
LETTERS TO THE EDITOR
467
tolerance to other drugs makes analgesia even more difficult. Recently, we treated a 49-yr-old man with intractable pain from a pelvic chondrosarcoma who demonstrated this problem. This patient had received maximal chemotherapy and, for more than a year, had used morphine at home through an intravenous pump. In the hospital, we failed to achieve analgesia or sedation with morphine infused at 1200 mglh or with hydromorphone at 800 mg/h. A midazolam infusion at 10 mg/h produced little effect. Finally, an intravenous infusion of ketamine, titrated to 2.7 mg.kg-'.h-', produced satisfactory pain relief while the patient remained awake. Unfortunately, we could not further refine this therapy because the patient died 30 h after starting ketamine. Current research on opioid receptors reveals three primary types-mu, kappa, and delta-and several subtypes of these. Ketamine acts at multiple thalamic and spinal cord sites, including opioid receptors (1).Ketamine also inhibits the dorsal horn nociceptive receptor stimulated by N-methyh-aspartic acid (NMDA) (2,3). That ketamine produced conscious analgesia in our opioid-tolerant patient may indicate it inhibited nociceptive pathways through NMDA receptor antagonism. The larger-than-normal ketamine requirement may indicate partial cross-tolerance with morphine, which occurs in animals (4). Perhaps ketamine or other NMDA antagonists will prove useful as adjuvant drugs in cancer patients receiving high doses of opioids. We would like to see more research or clinical reports in this area. Robert E. Johnstone, MD David J. Smith, PhD Department of Anesthesiology West Virginia University Health Sciences Center Morgantown, W V 26506
References Smith DJ, Pekoe GM, Monroe PJ, Martin LL, Cabral MEY, Crisp T. Ketamine analgesia in rats may be mediated by an interaction with opiate receptors. In: Domino EF, ed. Status of ketamine in anesthesiology. Ann Arbor: NPP Books, 1990199-209. Dubner R. Pain and hyperalgesia following tissue injury: new mechanisms and new treatments. Pain 1991;44:2134. Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-o-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293-9. Finck AD, Samaniego E, Ngai SH. Morphine tolerance decreases the analgesic effects of ketamine in mice. Anesthesiology 1988;68:397-400.
Complete Tolerance to Opioids
Is the "Kneeling" Prone Position as Dangerous as the Sitting Position for the Development of Venous Air Embolism?
To the Editor:
To the Editor:
Complete tolerance is a well-known, but rarely seen, complication of prolonged opioid administration. Aggressive pain management in cancer patients, who are living longer, is now presenting us with this clinical problem. Cross-
We are extremely impressed with the excellent report by Albin et al. (1) concerning major venous air embolism (VAE) occurring in three patients who were undergoing spinal surgery in the prone "kneeling" position. It would
investigation will be necessary to refine our understanding of the effects of EAA that we have reported in our study. Kenneth J. Tuman, MD Robert J. McCarthy, PharmD Anthony D. Ivankovich, MD Department of Anesthesiology Rush-Presbyterian-St. Luke's Medical Center Chicago, It 60622
References 1. Tuman KJ, McCarthy RJ, March RJ, DeLaria GA, Pate1 RV, Ivankovich AD. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 1991;73:696-704. 2. Christopherson R, Frank SM, Norris EJ, et al. Reoperation after lower extremity vascular surgery is more common after general than epidural anesthesia (abstract). Proceedings of the Society of Cardiovascular Anesthesia Annual Meeting, Boston, May 3, 1992.
Differential Awakening To the Editor: I would like to propose a new phenomenologic term, "differential awakening," for the clinical anesthesiologist. Over the years as a practicing neuroanesthesiologist, I and others have observed that patients with cerebral ischemia or mass lesions frequently show evolving lateralizing neurologic signs on awakening. Immediately on awakening, unilateral return of motor function is frequently delayed but improves, and returns to complete function over about 10-30 min, thus, the term "differential awakening." This process is clinically significant because it is clearly different from a surgical neurologic deficit that is expected to return slowly. It is also different from immediate surgical complications that might require reopening of the cranium or a computed axial tomographic scan for further diagnosis. Three theories could explain the phenomenon of differential awakening. First, anesthetics enter the brain and are trapped in areas that are injured by ischemia or trauma, and at the end of anesthesia, these anesthetics escape more slowly from the injured areas. Second, perhaps the areas of cerebral injury are more sensitive to low concentrations of the anesthetic, resulting in a slower unilateral emergence. Last, in patients who suffer destructive neurologic damage with full recovery, it is believed that secondary pathways compensate and accomplish the function of the destroyed neurons; perhaps these secondary pathways are only functional in a completely awake state. Roy F. Cucchiara, MD Department of Anesthesiology University of Florida College of Medicine Box 100254 Gainesville, FL 32620-0254
LETTERS TO THE EDITOR
467
tolerance to other drugs makes analgesia even more difficult. Recently, we treated a 49-yr-old man with intractable pain from a pelvic chondrosarcoma who demonstrated this problem. This patient had received maximal chemotherapy and, for more than a year, had used morphine at home through an intravenous pump. In the hospital, we failed to achieve analgesia or sedation with morphine infused at 1200 mglh or with hydromorphone at 800 mg/h. A midazolam infusion at 10 mg/h produced little effect. Finally, an intravenous infusion of ketamine, titrated to 2.7 mg.kg-'.h-', produced satisfactory pain relief while the patient remained awake. Unfortunately, we could not further refine this therapy because the patient died 30 h after starting ketamine. Current research on opioid receptors reveals three primary types-mu, kappa, and delta-and several subtypes of these. Ketamine acts at multiple thalamic and spinal cord sites, including opioid receptors (1).Ketamine also inhibits the dorsal horn nociceptive receptor stimulated by N-methyh-aspartic acid (NMDA) (2,3). That ketamine produced conscious analgesia in our opioid-tolerant patient may indicate it inhibited nociceptive pathways through NMDA receptor antagonism. The larger-than-normal ketamine requirement may indicate partial cross-tolerance with morphine, which occurs in animals (4). Perhaps ketamine or other NMDA antagonists will prove useful as adjuvant drugs in cancer patients receiving high doses of opioids. We would like to see more research or clinical reports in this area. Robert E. Johnstone, MD David J. Smith, PhD Department of Anesthesiology West Virginia University Health Sciences Center Morgantown, W V 26506
References Smith DJ, Pekoe GM, Monroe PJ, Martin LL, Cabral MEY, Crisp T. Ketamine analgesia in rats may be mediated by an interaction with opiate receptors. In: Domino EF, ed. Status of ketamine in anesthesiology. Ann Arbor: NPP Books, 1990199-209. Dubner R. Pain and hyperalgesia following tissue injury: new mechanisms and new treatments. Pain 1991;44:2134. Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-o-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293-9. Finck AD, Samaniego E, Ngai SH. Morphine tolerance decreases the analgesic effects of ketamine in mice. Anesthesiology 1988;68:397-400.
Complete Tolerance to Opioids
Is the "Kneeling" Prone Position as Dangerous as the Sitting Position for the Development of Venous Air Embolism?
To the Editor:
To the Editor:
Complete tolerance is a well-known, but rarely seen, complication of prolonged opioid administration. Aggressive pain management in cancer patients, who are living longer, is now presenting us with this clinical problem. Cross-
We are extremely impressed with the excellent report by Albin et al. (1) concerning major venous air embolism (VAE) occurring in three patients who were undergoing spinal surgery in the prone "kneeling" position. It would
