Mark S. Scheller

The importance of transtracheal jet ventilation in the management of the difficult airway

The Importance of Transtracheal Jet Ventilation in the Management of the Difficult Airway Jonathan Benumof;Mark Scheller; Anesthesiology

Changes in Extracellular Concentrations of Glutamate, Aspartate, Glycine, Dopamine, Serotonin, and Dopamine Metabolites After Transient Global Ischemia in the Rabbit Brain

Although considerable evidence supports a role for excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of ischemia on the extracellular concentrations of these agents. Recently, other neurotransmittiers (e.g., glycine and doparaine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, glycine concentrations in the hippocampus, and dopamine, serotonin, and dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brains extracellular space before, during, and after the ischemic period. Glutamate and aspartate concentrations in the dialysate increased from baseline by 1‐, 5‐, and 13‐fold and by 4‐, 9‐, and 31‐fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of glutamate and aspartate were significantly higher with increasing ischemic duration. Dopamine concentrations increased by approximately 700‐fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion. Glycine, in contrast, increased during ischemia by a mean of 4‐fold, but remained elevated throughout the 80‐min period of reperfusion. The final concentrations of glycine were significantly higher than baseline levels (p = 0.0002, Mann‐Whitney test). That glutamate and aspartate concentrations in the hippocampus co‐vary with the duration of global ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury. The observation that dopamine concentrations increased independently of ischemic duration indicates a maximal release with only S min of ischemia and suggests that dopamines role in the incremental injury seen with increasing ischemic duration is limited to prolonged high concentrations rather than increasing peak levels as seen with glutamate and aspartate. The sustained elevation of glycine concentrations after ischemia may explain the ability of excitatory amino acids to produce delayed toxicity in the reperfusion phase, as glycine has been shown to facilitate glutamates activity at the N‐ methyl‐D‐aspartate receptor.

MAC of sevoflurane in humans and the New Zealand white rabbit

The minimum alveolar concentration of sevoflurane necessary to prevent movement in 50 per cent of patients (MAC) was determined to be 2.05 per cent in 20 adult surgical patients. Because this value was higher than the only other experimentally determined human MAC value for sevoflurane (1.71 per cent), MAC was also determined in New Zealand white rabbits. Comparisons of the MAC ratios of sevoflurane to other volatile anaesthetics in both the human and the rabbit suggest that the human MAC value we obtained for sevoflurane is consistent with experimental determinations of MAC of other volatile anaesthetics in humans.RésuméLa concentration alvéolaire minimale du sévoflurane nécessaire afin de prévenir les mouvements dans 50 per cent des patients (MAC) a été déterminée à 2.05 per cent chez 20 patients adultes subissant une chirurgie. Etant donné que cette valeur était plus élevée que celle obtenue expérimentalement chez les humains avec le sévoflurane (1.71 per cent), le MAC a aussi a été déterminé chez les lapins blanc de la Nouvelle-Zélande. Des comparaisons des rapports de MAC entre le sévoflurane et ďautres agents anesthésiques volatiles tant chez ľhumain que chez le lapin suggèrent que les valeurs du MA C qu’on a obtenues chez ľhumain avec le sévoflurane sont comparables avec celles déterminées expérimentalement pour ďautres agents anesthésiques volatiles chez ľhomme.

Hypothermia prevents ischemia-induced increases in hippocampal glycine concentrations in rabbits.

We subjected 10 New Zealand White rabbits to 10 minutes of global cerebral ischemia under either normothermic (37 degrees C) or moderately hypothermic (29 degrees C) conditions. Hippocampal concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. Outcome was assessed by both neurological and neuropathologic criteria. Hypothermia afforded nearly complete protection from ischemic injury. Ischemia-induced increases in the concentrations of glutamate, aspartate, and glycine in the normothermic group (3, 12, and 3 times baseline) were strikingly attenuated in the hypothermic group. In addition, the prolonged postischemic elevation of glycine levels seen in the normothermic group was absent in the hypothermic group. These results suggest that the neuroprotective properties of hypothermia may reside, in part, in their ability to prevent increases in the extracellular concentrations of amino acids that enhance the activity of the N-methyl-D-aspartate receptor complex.

A multicenter comparison of maintenance and recovery with sevoflurane or isoflurane for adult ambulatory anesthesia

Sevoflurane was compared with isoflurane in 246 adult ASA class I-III patients undergoing ambulatory surgery. After administration of midazolam 1-2 mg and fentanyl 1 microgram/kg, anesthesia was induced with propofol 2 mg/kg and maintained with either sevoflurane or isoflurane in 60% nitrous oxide to maintain arterial blood pressure at +/- 20% of baseline. Fresh gas flows were 10 L/min during induction and 5 L/min during maintenance. Times to eye opening, command response, orientation, and ability to sit without nausea and/or dizziness were significantly faster after sevoflurane. Significantly more sevoflurane patients met Phase 1 of postanesthesia care unit (PACU) Aldrete recovery criteria (> or = 8) at arrival, 95% vs 81%. Also, significantly more sevoflurane patients were able to complete psychomotor recovery tests during the first 60 min postanesthesia. Discharge times were not different. Sevoflurane patients had significantly lower incidences of postoperative somnolence (15% vs 26%) and of nausea both in the PACU (36% vs 51%) and in the 24-h postdischarge period (9% vs 24%). Patient satisfaction was high overall (sevoflurane 97%, isoflurane 93%). We conclude that sevoflurane is a useful inhaled anesthetic for maintenance of ambulatory anesthesia.

The effects of sevoflurane on cerebral blood flow, cerebral metabolic rate for oxygen, intracranial pressure, and the electroencephalogram are similar to those of isoflurane in the rabbit

The effects of 0.5 and 1.0 MAC end-tidal concentrations of sevo-flurane on intracranial pressure, cerebral metabolic rate for oxygen, cerebral blood flow, and the electroencephalogram were compared to those of equi-MAC concentrations of isoflurane in rabbits anesthetized with morphine-nitrous oxide. At 1.0 MAC end-tidal level, both sevoflurane and isoflurane caused a significant reduction in cerebral metabolic rate for oxygen of about 50%. Neither anesthetic caused a significant change in global cerebral blood flow or cortical cerebral blood flow during either 0.5 or 1.0 MAC administration. However, both sevoflurane and isoflurane caused small but significant increases in intracranial pressure during 0.5 MAC and 1.0 MAC administration. The electroencephalogram of animals anesthetized with 1.0 MAC of either anesthetic demonstrated a burst suppression pattern with no evidence of spike or seizure activity. The data suggest that the effects of sevofluranc on cerebral blood flow, cerebral metabolic rate for oxygen, intracranial pressure, and the electroencephalogram are indistinguishable from those of equivalent concentrations of isoflurane in the rabbit.

Dexmedetomidine, an α2-adrenergic agonist, decreases cerebral blood flow in the isoflurane-anesthetized dog

The purpose of this study was to examine the effects of dexmedetomidine, an α2-adrenergic agonist, on cerebral blood flow and metabolic rate in dogs anesthetized with 0.64% isoflurane. After intubation and institution of mechanical ventilation, arterial, venous, pulmonary artery, and sagittal sinus catheters were inserted. Measurements of cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRo2), mean arterial pressure, cardiac output, and blood gas tensions were made at various levels of isoflurane anesthesia (0.64%, 1.9%, and 2.8%), after the administration of 10 μg/kg of dexmedetomidine (a dose that has been shown to reduce anesthetic requirements in dogs by >90%) and finally after 0.3 mg/kg of the α2-adrenergic antagonist idazoxan. Despite an increase in arterial pressure, dexmedetomidine caused a marked reduction (>45%, P < 0.05) in CBF when compared with all preceding concentrations of isoflurane. The administration of dexmedetomidine had no effect on the CMRo2. The electroencephalogram showed a loss of high-frequency activity in a pattern similar to that seen with 1.90% isoflurane. Administration of dexmedetomidine was associated with a 57% decrease in cardiac output (to 0.89 L/min). Administration of idazoxan (an α2-adrenergic antagonist) resulted in an increase in cardiac output and a reversal of the electroencephalogram effects. This experiment indicates that 10 μg/kg of dexmedetomidine in isoflurane-anesthetized dogs is associated with a profound decrease in CBF and cardiac output in the face of an unaltered CMRo2. Despite the large reduction in the CBF/CMRo2 ratio, there was no evidence of global cerebral ischemia.

Effect of a hypertonic lactated Ringer's solution on intracranial pressure and cerebral water content in a model of traumatic brain injury.

There has recently been an increased interest in the use of hypertonic solutions for fluid resuscitation of trauma victims. In this study, we examined the acute cerebral effects of a hypertonic lactated Ringers solution (measured osmolality = 469 mOsm/kg) in an animal model of traumatic brain injury. Following the production of a cerebral cryogenic lesion, eight New Zealand white rabbits were randomized to undergo hemodilution with either lactated Ringers (measured osmolality = 254 mOsm/kg) or hypertonic lactated Ringers. Over the course of the experiment the lactated Ringers group required significantly more fluid than the hypertonic group to maintain stable central venous and mean arterial pressure (245 +/- 5 ml vs. 132 +/- 20 ml; p less than 0.0001). Osmolality increased in the hypertonic group by 13.5 +/- 3.3 mOsm/kg whereas it decreased in the lactated Ringers group by 5.5 +/- 2.6 mOsm/kg. Intracranial pressure increased in both groups over the course of the experiment but the increase in pressure was greater in the lactated Ringers group than the hypertonic group (9.5 +/- 2.4 mm Hg vs. 1.7 +/- 1.5 mm Hg; p less than 0.001). Brain water content was significantly increased in the region of the lesion as assayed by both the wet/dry weight method and cortical specific gravity determinations, but there was no difference between the two treatment groups. Water content of the nonlesioned hemisphere was significantly less in the hypertonic group. This study suggests that hypertonic saline solutions may be useful for the resuscitation of hypovolemic patients with localized brain injury.

Effects of hypothermia or anesthetics on hippocampal glutamate and glycine concentrations after repeated transient global cerebral ischemia.

BackgroundThe search for cerebroprotective pharmacologic interventions has been based on the assumption that reducing the cerebral metabolic rate may enhance the cerebral tolerance for ischemic episodes. Recently, evidence has accumulated implicating excitatory amino acids (e.g., glutamate) as mediators of ischemic brain injury. We investigated the effects of mild hypothermia (32° C), pentobarbital, isoflurane, and propofol on hippocampal extracellular concentrations of glutamate and glycine after repeated global ischemia. MethodsNew Zealand white rabbits were initially anesthetized with halothane in oxygen. Brain epidural temperature was reduced by external cooling in the hypothermia group to 32° C (n = 5). A burst-suppressed electroencephalogram pattern was achieved in the other groups with isoflurane (n = 7), pentobarbital (n = 6), or propofol (n = 6). Halothane-anesthetized rabbits (1% inspired) served as the control group (n = 5). In all groups, two global cerebral ischemic episodes (each 7.5 min) were produced by a combination of neck tour niquet inflation and induction of systemic hypotension. Perlischemic hippocampal glutamate and glycine concentrations were estimated using in vivo microdialysis and high-performance liquid chromatography (two-way analysis of variance, P < 0.05). ResultsGlutamate concentrations were similar in the five groups during the baseline period. Hypothermia (32° C) was associated with significantly lower concentrations of glutamate during both the first and second ischemic periods when compared with all other groups. Although there were no differences in glycine concentrations among groups during the first ischemic episode, glycine concentrations were significantly lower in the hypothermic group compared with the control, isoflurane, and pentobarbital groups during the second episode of cerebral ischemia. Glycine concentrations also were lower in the propofol group when compared to the isoflurane and pentobarbital groups. ConclusionsHypothermia (32° C) attenuates ischemia-induced increases in both glutamate and glycine concentrations after repeated global cerebral ischemia. Propofol attenuated glycine increases in a manner similar to that of hypothermia but did not attenuate ischemia-induced glutamate increases. There were no differences in hippocampal glutamate or glycine concentrations for animals receiving isoflurane, halothane, or pentobarbital.

A Comparison of the Direct Cerebral Vasodilating Potencies of Halothane and Isoflurane in the New Zealand White Rabbit

Halothane is commonly viewed as a more potent cerebral vasodilator than isoflurane. It was speculated that the lesser vasodilation caused by isoflurane might be the result of the greater reduction in cerebral metabolic rate (CMR) that it causes, and that the relative vasodilating potencies of halothane and isoflurane would be similar if the two agents were administered in a situation that precluded volatile-agent-induced depression of CMR. To test this hypothesis, cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMR01) were measured in two groups of rabbits before and after the administration of 0.75 MAC halothane or isoflurane. One group received a background anesthetic of morphine and N2O, which resulted in an initial CMR01 of 3.21 ± 0.17 (SEM) ml · 100 g−1 · min−1; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMR01 of 1.76 ± 0.16 ml · 100 g−1 · min−1. In rabbits receiving a background of morphine sulfate/ N2O, halothane resulted in a significantly greater CBF (65 ± 10 ml · 100 g−1 · min−1) than did isoflurane (40 ± 5 ml · 100 g−1 · min−1). Both agents caused a reduction in CMRO1, but CMRO1 was significantly less during isoflurane administration. By contrast, with a background of pentobarbital anesthesia, CBF increased by significant and similar amounts with both halothane and isoflurane. With halothane, CBF increased from 22 ± 2 ml · 100 g−1 · min−1 in the control state to 39 ± 3, and with isoflurane from 24 ± 2 to 38 ± 2 ml · 100 g−1 · min−1. CMR01 was not depressed further by either halothane or isoflurane. These results suggest that the relative effects of halothane and isoflurane on CBF are dependent on the CMR present prior to their administration. When the preexistent CMR is not markedly depressed, isoflurane decreases CMR and causes less cerebral vasodilation than does halothane. When initial CMR is depressed, halothane and isoflurane have similar vasodilating potencies.