Joseph F. Antognini

Exaggerated Anesthetic Requirements in the Preferentially Anesthetized Brain

BackgroundThe brain is assumed to be the site of anesthetic action, but anesthetics have effects elsewhere, such as the spinal cord. A preferentially anesthetized goat brain model was used to determine the importance of anesthetic action in the brain. MethodsSix goats were anesthetized with isoflurane; after tracheal intubation and insertion of a femoral arterial catheter, bilateral neck dissections were performed to isolate the external carotid arteries and external jugular veins. The occipital arteries were ligated to prevent vertebral blood from entering the carotid system. (Goats do not have direct, significant vertebral artery contributions to the brain, and they lack internal jugular veins.) Control Isoflurane minimum alveolar concentration (MAC) was determined using a dew-claw clamp as the painful stimulus. Following this, cranial venous blood was drained into a bubble oxygenator in which an isoflurane vaporizer was placed in line with the gas flow. Oxygenator arterial isoflurane concentration was estimated from the Isoflurane partial pressure in the oxygenator exhaust. Isoflurane administration via the lungs was discontinued and the isoflurane partial pressure in the blood delivered via the carotid artery was Increased by an amount required to bracket the partial pressures permitting and preventing movement in response to dew-claw stimulation. The native circulation was reestablished and MAC determined again. ResultsCerebral Isoflurane requirements were 1.2 ± 0.3% (mean ± SD) before bypass, increased to 2.9 ± 0.7% during bypass when the brain was preferentially anesthetized, and decreased to 1.3 ± 0.1% after bypass. ConclusionsThe results support the importance of sub-cortical structures, such as the spinal cord, in the generation of purposeful movement in response to a painful stimulus under general anesthesia.

Inhaled anesthetics and immobility: Mechanisms, mysteries, and minimum alveolar anesthetic concentration

Studies using molecular modeling, genetic engineering, neurophysiology/pharmacology, and whole animals have advanced our understanding of where and how inhaled anesthetics act to produce immobility (minimum alveolar anesthetic concentration; MAC) by actions on the spinal cord. Numerous ligand- and voltage-gated channels might plausibly mediate MAC, and specific animo acid sites in certain receptors present likely candidates for mediation. However, in vivo studies to date suggest that several channels or receptors may not be mediators (e.g., &ggr;-aminobutyric acid A, acetylcholine, potassium, 5-hydroxytryptamine-3, opioids, and &agr;2-adrenergic), whereas other receptors/channels (e.g., glycine, N-methyl-d-aspartate, and sodium) remain credible candidates.

Does the Brain Influence Somatic Responses to Noxious Stimuli during Isoflurane Anesthesia

Background:Recent evidence suggests that anesthetic action within the spinal cord is important in suppressing somatic responses to painful stimuli. Whether the brain influences this response is not clear. This study was designed to test the hypothesis that the brain affects anesthetic requirements. Methods:Six goats were anesthetized with isoflurane. After tracheal intubation and femoral arterial cannulatlon, bilateral neck dissections were performed to isolate the external carotid arteries and external jugular veins. The occipital arteries were ligated bilaterally. Control isoflurane requirements as defined by the minimum alveolar concentration (MAC) were determined by using a dew-claw clamp as a painful stimulus. Cranial venous blood was drained into a bubble oxygenator in which an isoflurane vaporizer was placed in line with the gas flow, and arterial blood was infused into a carotid artery with a roller pump. This arrangement permitted selective control of the delivery of anesthetic to the head and to the systemic circulation. Isoflurane concentration in the arterial blood delivered to the head was estimated from the isoflurane concentration in the oxygenator exhaust. While isoflurane concentration in the head was maintained at approximately 0.2- 0.3%, MAC for the body was determined. After return to the native circulation, MAC was determined again. Results:During bypass with cranial isoflurane concentration at 0.2-0.3%, all animals showed varying, intermittent degrees of light anesthesia, including spontaneous head movement, chewing, swallowing, and eye opening. Isoflurane MAC was 1.4 ± 0.2% (mean ± SD) at baseline, decreased to 0.8 ± 0.1% during bypass (P < 0.05), and increased to 1.2 ± 0.2% after bypass (P not significant compared with baseline). Conclusions:These results verify the importance of volatile anesthetic action at an extracranial site vis à vis purposeful movement in response to a noxious stimulus. Furthermore, the results confirm that the brain affects anesthetic requirements.

Perioperative drug therapy in elderly patients.

Advances in modern medicine and public health have resulted in increased longevity, which in turn has resulted in more elderly patients (arbitrarily defined as aged 65 yr or older) coming to the operating room for a variety of surgical procedures. Even in the absence of comorbidities, these patients, as compared with their younger cohorts, respond differently to various perioperative physiologic trespasses and pharmacologic interventions. In this clinical commentary, we focus on the altered pharmacologic responses elderly patients have during the perioperative period. In many instances, elderly patients are more sensitive to drugs, and for the purposes of this clinical commentary, we use the word sensitivity in its general clinical meaning, i.e., an enhanced response for a given dose of drug that might have a pharmacokinetic or pharmacodynamic explanation.

Peri-MAC Depression of a Nociceptive Withdrawal Reflex Is Accompanied by Reduced Dorsal Horn Activity with Halothane but not Isoflurane

Background Anesthetics act in the spinal cord to suppress movement evoked by a noxious stimulus, although the exact site is unknown. Methods This study investigated sensorimotor processing in hind limb withdrawal reflexes, and effects of two general anesthetics, halothane and isoflurane, on simultaneously recorded responses of single dorsal horn neurons and hind limb withdrawal force, elicited by graded noxious thermal hind paw stimulation in rats. Minimum alveolar anesthetic concentration (MAC) needed to block gross movement to a supra-maximal mechanical stimulus was determined for each animal. Results Between 0.9 and 1.1 MAC, halothane and isoflurane greatly reduced or abolished withdrawal force (79 and 89% reduction, respectively). Halothane (0.75–1.4 MAC) depressed heat-evoked neuronal responses in a concentration-related manner (41% reduction between 0.9 and 1.1 MAC averaged across all stimulus temperatures, P < 0.05) and decreased stimulus-response function slopes, with corresponding reductions in withdrawal force. In contrast, isoflurane did not reduce neuronal responses in the 0.75–1.4 MAC range and slightly facilitated responses (by 16%) when concentration increased from 0.9 to 1.1 MAC, despite a concurrent withdrawal force reduction. Anesthetic depression of heat-evoked withdrawal force correlated well with MAC determination using a supra-maximal mechanical stimulus. At sub-MAC anesthetic concentrations, some units exhibited firing rate changes that preceded and paralleled moment-to-moment changes in force during a given withdrawal. Conclusions Halothane reduces noxious-evoked movement at least partly via depression of dorsal horn neurons, whereas isoflurane suppresses movement by an action at more ventral sites in the spinal cord.

Somatosensory cortex: A comparison of the response to noxious thermal, mechanical, and electrical stimuli using functional magnetic resonance imaging

In the present study, functional magnetic resonance imaging (fMRI) was used to examine pain perception in humans. Three types of noxious stimuli were presented: electric shock (20.8 mA, 2 Hz), heat (48°C), and mechanical, as well as a control tactile stimulus. The significance of activation at the level of the voxel was determined using correlation analysis. Significant region of interest (ROI) activation was determined by comparing the percentage of active voxels in each ROI to activation in a control ROI in the visual cortex. In response to tactile and shock stimuli, consistent activation was seen in the postcentral gyrus, parietal operculum, and ipsilateral cerebellar cortex. No significant cortical activation was detected in response to noxious heat or mechanical stimulation when compared to nonpainful intensity levels. The data did not indicate adaptation, although further study in this area is necessary. Stationary noxious thermal and mechanical stimulation are “pure” noxious stimuli, while electrical stimulation influenced nociceptive and nonnociceptive receptors. Lack of detectable activation in response to pure noxious stimuli supports the idea that nociceptive and nonnociceptive fibers are interspersed in the somatosensory cortex. Conflicting results from recent functional imaging studies of pain perception regarding cortical activation indicate that it is essential to consider both the tactile and nociceptive components of the stimuli used, the spatial extent of stimulation, and the possibility of adaptation to the response. Furthermore, these results suggest that subtractive or correlative methods may not be sufficiently sensitive to image the activity of nociceptive cells, which are sparsely distributed throughout the somatosensory cortex. Hum. Brain Mapping 6:150–159, 1998.

Hypothermia Eliminates Isoflurane Requirements at 20° C

Background:Hypothermia decreases anesthetic requirements, but the temperature that completely eliminates anesthetic needs has not been previously etermined. Methods:Eight female goats were anesthetized with isoflurane and catheters were placed in the femoral artery and cranial vena cava, after which the right carotid artery and external jugular vein were dissected free. Peripheral temperature was monitored in the rectum and core temperature in the vena cava. A thermistor was placed in the epldural space via a small burr hole to monitor brain temperature. Minimum alveolar concentration (MAC) for isoflurane was determined by eliciting gross, purposeful movement with a tall clamp. Cardiopulmonary bypass (CPB) was established using bubble oxygenators with venous blood drained from a jugular vein and arterial blood infused with a roller pump into the carotid artery. The animals were cooled to approximately 29° C, and MAC redetermlned, after which further cooling to 20° C was accomplished. Isoflurane was eliminated, core and brain temperature adjusted in 2-3° C increments, and the tail clamp applied until two temperatures were found that just permitted and just prevented movement. The animals were rewarmed, isoflurane added, and post-CPB MAC determined. Results:At 38.5° C, pre-CPB MAC was 1.3 ± 0.1% (mean ± SEM). At 29.0° C, MAC was 0.7 ± 0.1%, and the anesthetizing temperature was 20.1 ± 0.6° C. At 37.3° C, post-CPB MAC was 1.0 ± 0.1% (P<0.05 vs. pre-CPB). Conclusions:These results confirm the rectilinear decrease in MAC seen in previous studies and establishes the anesthetizing temperature at 20° C.

Isoflurane anesthesia blunts cerebral responses to noxious and innocuous stimuli: a fMRI study

We used functional magnetic resonance imaging to determine how isoflurane affected cerebral neuronal activation resulting from noxious and innocuous stimuli. Five male volunteers were subjected to mild electrical shock and tactile stimuli applied to the hand. During low (0.7%) and moderate (1.3%) isoflurane anesthesia the stimuli were repeated and a supramaximal electrical shock was also applied. Tactile stimulation activated bilateral SI and SII, but resulted in no significant activation at low or moderate anesthesia. Electrical shock activated contralateral SI and bilateral SII; low anesthesia completely abolished this response. The supramaximal stimulus activated the caudate nucleus and bilateral thalamus at low anesthesia; these responses were diminished at moderate anesthesia. Isoflurane anesthesia blunts cerebral responses to somatosensory stimuli, and the absence of cortical activation during supramaximal stimulation suggests that noxious-induced movement is generated in lower CNS structures.

Safety of regional anesthesia in Eisenmenger's syndrome.

Background and Objectives Eisenmenger’s syndrome is characterized by right-to-left or bidirectional shunting and pulmonary hypertension. Perioperative risk is high for noncardiac surgery, and many clinicians avoid regional anesthesia because of the potential deleterious hemodynamic effects. We determined perioperative mortality based on published reports describing anesthetic management in patients with Eisenmenger’s syndrome. Methods A literature search identified 57 articles describing 103 anesthetics in patients with Eisenmenger’s syndrome. An additional 21 anesthetics were identified in patients receiving regional anesthesia for labor. Results Overall perioperative mortality was 14%; patients receiving regional anesthesia had a mortality of 5%, whereas those receiving general anesthesia had a mortality of 18%. This trend favored the use of regional anesthesia but was not statistically significant. A better predictor of outcome was the nature of the surgery (and presumably the surgical disease). Patients requiring major surgery had mortality of 24%, whereas those requiring minor surgery had mortality of 5% (P < .05). Patients in labor receiving regional anesthesia had a mortality rate of 24%, and most of these occurred several hours after delivery. Conclusions This review of anesthesia and surgery in patients with Eisenmenger’s syndrome reveals that most deaths probably occurred as a result of the surgical procedure and disease and not anesthesia. Although perioperative and peripartum mortalities are high, many anesthetic agents and techniques have been used with success.

Anaesthesia for Charcot-Marie-Tooth disease: a review of 86 cases

Operative charts were reviewed in 86 patients with Charcot-Marie-Tooth disease, a condition characterized by chronic muscular denervation. A total of 161 surgical procedures was performed. Major complications were few, and only one operative death occurred, unrelated to anaesthesia. Succinylcholine and malignant hyperthermia triggering agents were used in 41 (48%) and 77 (90%) patients, respectively, without untoward effects. Contrary to previous reports, this survey supports the safe use of succinylcholine and MH triggering agents in this disease.RésuméLa maladie de Charcot-Marie-Tooth se caractérise par une dénervation musculaire chronique. Les dossiers anesthésiques de 86 patients atteints de cette maladie ont été revus. Les patients avaient subi un total de 161 interventions chirurgicales. Il y à eu peu de complications majeures, et un seul décès périopératoire sans relation avec l’anesthésie. La succinylcholine a été utilisée chez 41 (48%) patients et d’autres agents susceptibles d’induire une hyperthermie maligne ont servi pour anesthésier 77 (90%) patients. Aucun effet indésirable dû à ces médicaments n’a été observé. Contrairement à d’autres observations cliniques, cette étude rétrospective suggère que la succinylcholine et les agents inducteurs d’hyperthermie maligne peuvent être utilisés sans augmenter le risque de complication chez les patients atteints de cette maladie.