The connection between Dr. Harold Griffith and Richard Gill: new insights into the history of curare use in anesthesia from previously unknown correspondence.

Dr. Harold R. Griffith and Richard C. Gill figure prominently in curare's storied history. In 1938, Gill returned from an Amazon expedition with over 11 kg of curare. After scientists at E. R. Squibb & Sons identified a plant source (Chondrodendron tomentosum) and isolated a stable extract of uniform potency (marketed as Intocostrin), Griffith administered it in the operating room in 1942, showing its advantages and safety. In this article, we report correspondence between Griffith and Gill, heretofore not appreciated, after finding a letter from Gill to Griffith affixed to the inside back cover of a book contained in a private library.Following the serendipitous discovery of this previously unknown letter, we interrogated archived correspondence and material associated with Griffith and Gill in the Osler Library History of Medicine (McGill University, Montreal, QC, Canada), Arthur E. Guedel Memorial Anesthesia Center (University of California, San Francisco, CA, USA), the Wood Library Museum of Anesthesiology (Schaumburg, IL, USA), the Anaesthesia Heritage Centre (London, UK), and the Wellcome Collection (London, UK). Further, we searched for information on the historical background of curare via Google, Ovid MEDLINE, Adam Matthew Explorer, Project MUSE, and Latin American History databases.We found seven letters. The first is a letter to Gill dated 2 June 1943 (Wood Library) and an earlier draft dated 2 June 1943 (Osler Library). In this letter, Griffith praises Gill's success in procuring curare and informs him of its usefulness in anesthesia. The second letter is a letter from Gill to Griffith dated 10 July 1943 (found affixed to a book that was donated to the Osler Library). In this letter, Gill congratulates Griffith and claims he foresaw curare's use in the operating room and predicts its routine use to produce muscle relaxation during surgery. The third letter is a letter to Griffith dated 17 April 1945 (Osler Library). In this correspondence, Gill disputes Squibb's claim that curare derives solely from C. tomentosum and asks Griffith to retract published statements on this point. The fourth letter is a letter to Gill dated 25 April 1945 (Osler Library), in which Griffith declines to retract and emphasizes that Gill receive credit for making curare available to medicine. The fifth letter is a letter to Griffith dated 24 May 1945 (Osler Library), in which Gill accepts Griffith's retraction decision and indicates negotiations with another drug company. The sixth letter is a letter to Griffith dated 11 July 1945 (Osler Library), in which Gill requests anesthesia morbidity and mortality data and continues to remonstrate against Squibb's claim of curare's botanical source. The seventh and final letter is to Gill and dated 21 July 1945 (Osler Library). In this letter, Griffith indicates the lack of morbidity and mortality information, mentions a new Squibb curare product, and cites data suggesting curare may exert dose-dependent CNS effects.These seven letters between Dr. H. Griffith and R. Gill reveal a professional relationship heretofore not appreciated. We discuss and consider these letters in the context of curare's remarkable history.

RéSUMé: Le Dr Harold R. Griffith et Richard C. Gill occupent une place importante dans l'histoire du curare. En 1938, Gill revient d'une expédition en Amazonie avec plus de 11 kg de curare. Après l'identification, par les scientifiques de E. R. Squibb & Sons, d'une source végétale (Chondrodendron tomentosum) et l'isolement d'un extrait stable de puissance uniforme (commercialisé sous le nom d'Intocostrin), Griffith l'administre en salle d'opération en 1942, montrant ses avantages et son innocuité. Dans cet article, nous résumons la correspondance entre Griffith et Gill, jusque-là peu appréciée, après avoir trouvé une lettre de Gill à Griffith glissée à l'intérieur de la quatrième de couverture d'un livre provenant d'une bibliothèque privée.À la suite de la découverte fortuite de cette lettre jusque-là inconnue, nous avons consulté la correspondance et les documents archivés associés à Griffith et Gill à la bibliothèque Osler History of Medicine (Université McGill, Montréal, QC, Canada), au centre Arthur E. Guedel Memorial Anesthesia Center (Université de Californie, San Francisco, CA, États-Unis), au Wood Library Museum of Anesthesiology (Schaumburg, IL, États-Unis), au Anaesthesia Heritage Centre (Londres, Royaume-Uni) et à la Wellcome Collection (Londres, Royaume-Uni). De plus, nous avons recherché des informations sur le contexte historique du curare via Google, Ovid MEDLINE, Adam Matthew Explorer, Project MUSE et dans les bases de données d'histoire de l'Amérique latine.Nous avons trouvé sept lettres. La première est une lettre à Gill datée du 2 juin 1943 (bibliothèque Wood) et une ébauche antérieure datée du 2 juin 1943 (bibliothèque Osler). Dans cette lettre, Griffith fait l'éloge du succès de Gill dans l'obtention du curare et l'informe de son utilité en anesthésie. La deuxième lettre est une lettre de Gill à Griffith datée du 10 juillet 1943 (trouvée collée dans un livre donné à la bibliothèque Osler). Dans cette lettre, Gill félicite Griffith et affirme qu'il avait pressenti l'utilisation du curare en salle d'opération et prédit son utilisation de routine pour produire une relaxation musculaire pendant la chirurgie. La troisième lettre est une lettre à Griffith datée du 17 avril 1945 (bibliothèque Osler). Dans cette missive, Gill conteste l'affirmation de Squibb selon laquelle le curare est exclusivement dérivé de C. tomentosum et demande à Griffith de se rétracter sur les déclarations publiées à ce sujet. La quatrième lettre est une lettre à Gill datée du 25 avril 1945 (bibliothèque Osler), dans laquelle Griffith refuse de se rétracter et insiste sur le fait que Gill soit crédité d'avoir mis le curare à la disposition de la médecine. La cinquième missive est une lettre à Griffith datée du 24 mai 1945 (bibliothèque Osler), dans laquelle Gill accepte la décision de Griffith de se rétracter et indique des négociations avec une autre compagnie pharmaceutique. La sixième lettre est une lettre à Griffith datée du 11 juillet 1945 (bibliothèque Osler), dans laquelle Gill demande des données concernant la morbidité et la mortalité liées à l'anesthésie et continue de protester contre l'affirmation de Squibb sur la source botanique du curare. La septième et dernière lettre est adressée à Gill et datée du 21 juillet 1945 (bibliothèque Osler). Dans cette lettre, Griffith indique le manque d'informations sur la morbidité et la mortalité, mentionne un nouveau produit à base de curare de Squibb et cite des données suggérant que le curare pourrait exercer des effets dose-dépendants sur le SNC.Ces sept lettres entre le Dr H. Griffith et R. Gill révèlent une relation professionnelle jusque-là peu appréciée. Nous discutons et considérons ces lettres dans le contexte de l'histoire remarquable du curare.

Migration of an Inferior Vena Cava Tumor Thrombus during Renal Cell Carcinoma Resection.

Approximately 4%-10% of patients with renal cell carcinoma (RCC) have tumoral vascular invasion with resultant thrombi in the renal vein and in the inferior vena cava (IVC). The authors describe an interesting case of IVC tumor thrombus that migrated to the right cardiac chambers during RCC resection. The diagnosis was made by intraoperative transesophageal echocardiography (TEE), which revealed the presence of a free-floating thrombus between the right atrium (RA) and right ventricle (RV). The patient required an urgent sternotomy with cardiopulmonary bypass (CPB) for atrial thrombus removal prior to the completion of the nephrectomy. The patient made a full recovery and was discharged to a rehabilitation facility. These findings illustrate the importance of intraoperative TEE monitoring during nephrectomy and IVC thrombectomy. In this case, TEE allowed for the diagnosis of an unexpected complication necessitating prompt cardiac surgical management.

Postoperative hypotonia in a patient with stiff person syndrome: a case report and literature review.

PURPOSE: Stiff person syndrome (SPS), an autoimmune disease that manifests with episodic muscle rigidity and spasms, has anesthetic considerations because postoperative hypotonia may occur. This hypotonia has been linked to muscle relaxants and volatile anesthetics and may persist in spite of neostigmine administration and train-of-four (TOF) monitoring suggesting full reversal. We present a patient with SPS who experienced hypotonia following total intravenous anesthesia (TIVA), which was promptly reversed with sugammadex. These observations are considered in light of the relevant medical literature. CLINICAL FEATURES: A 46-yr-old female patient with SPS underwent breast lumpectomy and sentinel node biopsy. Anesthesia consisted of TIVA (propofol/remifentanil) with adjunctive administration of rocuronium 20 mg to obtain adequate intubating conditions. Despite return of the TOF ratio to 100% within 30 min, hypotonia was clinically evident at conclusion of surgery two hours later. Sugammadex 250 mg reversed residual muscle relaxation permitting uneventful extubation. A literature review identified six instances of postoperative hypotonia (TIVA, n = 3; volatile anesthetics, n = 3) in spite of neostigmine administration (n = 2) and TOF monitoring suggesting full reversal (n = 4). CONCLUSIONS: Patients with SPS may show hypotonia regardless of general anesthetic technique (TIVA vs inhalational anesthesia), which can persist despite recovery of the TOF ratio and may be more effectively reversed by a chelating agent than with an anticholinesterase. If general anesthesia is required, we suggest a cautious approach to administering muscle relaxants including using the smallest dose necessary, considering the importance of clinical assessment of muscle strength recovery in addition to TOF monitoring, and discussing postoperative ventilation risk with the patient prior to surgery.

RéSUMé: OBJECTIF: Le syndrome de la personne raide (SPR), une maladie auto-immune qui se manifeste par une rigidité musculaire et des spasmes épisodiques, requiert certaines considérations anesthésiques en raison du risque d'hypotonie postopératoire. Cette hypotonie a été liée à des myorelaxants et à des anesthésiques volatils et peut persister malgré l'administration de néostigmine et un monitorage du train-de-quatre (TDQ) suggérant une neutralisation complète. Nous présentons le cas d'une patiente atteinte de SPR qui a souffert d'hypotonie après une anesthésie intraveineuse totale (TIVA), laquelle a été rapidement neutralisée à l'aide de sugammadex. Ces observations sont examinées à la lumière de la littérature médicale pertinente. CARACTéRISTIQUES CLINIQUES: Une patiente de 46 ans atteinte de SPR a bénéficié d'une tumorectomie mammaire et d'une biopsie du ganglion sentinelle. L'anesthésie consistait en une TIVA (propofol/rémifentanil) avec administration d'appoint de 20 mg de rocuronium pour atteindre des conditions d'intubation adéquates. Malgré le retour du ratio de TdQ à 100 % dans les 30 minutes, l'hypotonie était cliniquement évidente à la fin de la chirurgie deux heures plus tard. L'administration de 250 mg de sugammadex a neutralisé la relaxation musculaire résiduelle, permettant une extubation sans incident. Une revue de la littérature a identifié six cas d'hypotonie postopératoire (TIVA, n = 3; anesthésiques volatils, n = 3) malgré l'administration de néostigmine (n = 2) et le monitorage du TdQ suggérant une neutralisation complète (n = 4). CONCLUSION: Les patients atteints de SPR peuvent présenter une hypotonie quelle que soit la technique d'anesthésie générale utilisée (TIVA vs anesthésie par inhalation), laquelle peut persister malgré la récupération du rapport de TdQ; cette hypotonie peut être plus efficacement neutralisée par un agent chélateur qu'avec un anticholinestérasique. Si une anesthésie générale est nécessaire, nous suggérons une approche prudente pour l'administration de myorelaxants, y compris l'utilisation de la plus petite dose nécessaire, la prise en compte de l'importance de l'évaluation clinique de la récupération de la force musculaire en plus du monitorage du TdQ, et la communication du risque de ventilation postopératoire au patient avant la chirurgie.

Opioid-receptor antagonism increases pain and decreases pleasure in obese and non-obese individuals.

RATIONALE: Endogenous opioids inhibit nociceptive processing and promote the experience of pleasure. It has been proposed that pain and pleasure lie at opposite ends of an affective spectrum, but the relationship between pain and pleasure and the role of opioids in mediating this relationship has not been tested. OBJECTIVES: Here, we used obese individuals as a model of a dysfunctional opioid system to assess the role of the endogenous opioid peptide, beta-endorphin, on pain and pleasure sensitivity. METHODS: Obese (10M/10F) and age- and gender-matched non-obese (10M/10F) controls were included in the study. Pain sensitivity using threshold, tolerance, and subjective rating assessments and perceived sweet pleasantness using sucrose solutions were assessed in two testing sessions with placebo or the opioid antagonist, naltrexone (0.7 mg/kg body weight). Beta-endorphin levels were assessed in both sessions. RESULTS AND CONCLUSIONS: Despite having higher levels of baseline beta-endorphin and altered beta-endorphin-reactivity to naltrexone, obese individuals reported a similar increase in pain and decrease in pleasantness following naltrexone compared to non-obese individuals. Beta-endorphin levels did not correlate with pain or pleasantness in either group, but naltrexone-induced changes in pain and pleasantness were mildly correlated. Moreover, naltrexone-induced changes in pain were related to depression scores, while naltrexone-induced changes in sweet pleasantness were related to anxiety scores, indicating that pain and pleasantness are related, but influenced by different processes.

Broken heart syndrome triggered by an obstructive goiter not associated with thyrotoxicosis.

PURPOSE: Takotsubo cardiomyopathy (TC) is described as transient ventricular dysfunction following emotional or physical trauma. A few reports have described patients with TC in association with various circumstances of thyrotoxicosis. We report an unusual case of TC in a patient with a large retrosternal goiter and normal thyroid function. We speculate that TC was triggered by compromise of tracheal flow induced by the goiter. CLINICAL FEATURE: A 68-yr-old woman without primary heart disease presented with cardiorespiratory collapse requiring ventilatory and cardiovascular support, including placement of an intra-aortic balloon pump. She was diagnosed with a severe form of TC based on characteristic echocardiography findings and clinical course. Within less than a week, her myocardial function completely normalized. The patient was later found to have a large retrosternal goiter compressing her trachea, though her thyroid function was normal. A total thyroidectomy was eventually performed, and she made a full recovery. Subsequently, the patient was found to have a positive JAK2 mutation for a myeloproliferative disorder. CONCLUSIONS: Takotsubo cardiomyopathy may be regarded as the final common pathway of cardiac dysfunction triggered by various stress conditions, in this case, a large retrosternal goiter not associated with thyrotoxicosis and likely exacerbated by severe leukocytosis related to a myeloproliferative disorder.

Epidural blood patch in a patient with multiple sclerosis: is it safe?

PURPOSE: Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system resulting in demyelination and axonal injury. Epidural blood patch (EBP) to treat postdural puncture headache (PDPH) in an MS patient may be of concern because of the potential for this to interfere with axonal conduction. Even with normal axons, pressure can interfere with impulse conduction, and it is unknown whether affected axons of the MS patient are particularly vulnerable to the increase in epidural pressure that occurs as a consequence of the EBP. We describe our experience with EBP in an MS patient. While peridural pressure changes were not measured, we attempted to quantify any pressure-induced interference with axonal conduction by measuring changes in somatosensory evoked responses. CLINICAL FEATURES: A 50-yr-old female MS patient required an EBP for a PDPH after a diagnostic lumbar puncture. The first EBP (20 mL autologous blood, L3-4 interspace) was followed by a transient improvement in PDPH and then a worsening with increased lower-extremity weakness. A second EBP was performed (12 mL autologous blood, L3-L4 interspace) with concomitant evoked potential recordings (stimulating electrodes over the left posterior tibial nerve and recording electrodes at CZ-FZ coordinates). Postdural puncture headache symptoms were permanently relieved, and the effects of the EBP on evoked P40 latency responses (39.7 msec and 44.3 msec pre- and post-EBP, respectively) were considered to be physiologically insignificant. CONCLUSION: A report of EBP to treat PDPH in an MS patient is presented. We postulate that this type of patient may be at risk for impaired conduction of impulses in affected axons due to the increase in pressure produced by epidural injection of blood. Literature review indicates that pressure increases may be reduced by injecting the blood slowly. When EBP is considered in patients with axon conduction deficits, consideration should be given to concomitant monitoring of somatosensory evoked responses to help quantify interference with axonal conduction as a consequence of injection of blood into the epidural space.

Montreal's contribution to the Quebec anesthesia workforce: a comparison between anesthesia residents trained at McGill University and those trained at Université de Montréal.

PURPOSE: Alumni from McGill University (MAA) and alumni from Université de Montréal (UMA) anesthesia residency programs were compared with regard to demographic characteristics and practice location. METHODS: McGill University alumni and UMA (1990-2010) were studied according to age, sex, pre-anesthesia education, fellowship training, advanced research training, and practice location. Logistic regression analysis of demographics in relation to practice location was performed. RESULTS: Alumni were mostly male (MAA [n = 102]; male:female 72 [71%]: 30 [29%] vs UMA [n = 89]; male:female 51 [57%]: 38 [43%]) in their early thirties [mean 32; standard deviation (3.2) and 32 (3.0), respectively]. Approximately 45% of MAA obtained an undergraduate education in provinces other than Quebec compared with 6% of UMA. A majority of alumni from either institution practice in Quebec (MAA 67%; UMA 94%). Of the MAA who received undergraduate education in Quebec, approximately 80% practice in that province compared with approximately 46% of those who were educated in other provinces. Fellowship training for MAA who work in Quebec or in other provinces was similar (68%). About one-third (33%) of UMA who work in Quebec obtained fellowship training. All alumni who received undergraduate education abroad (MAA n = 9; UMA n = 1) practice in Quebec. Three MAA and one UMA practice in the USA. Regression analysis suggests that working in Quebec is associated with obtaining an undergraduate medical education in that province (odds ratio 4.3; 95% confidence interval 1.1 to 21.2). CONCLUSIONS: The majority of MAA and UMA practice in Quebec, particularly if they received their undergraduate education there. Residents educated (undergraduate) in the rest of Canada are more likely to practice in other provinces. Residents with undergraduate education from abroad are highly likely to practice anesthesia in Quebec. A small portion of alumni elect to practice anesthesia in the USA.

Combined heart and liver transplantation on cardiopulmonary bypass: report of four cases.

PURPOSE: Combined heart and liver transplant is a rare procedure to treat end-stage cardiac and liver disease. First performed during cardiopulmonary bypass and anticoagulation, subsequent concerns about increased bleeding changed the strategy to performing liver implantation following separation from cardiopulmonary bypass. Considering the overall decrease in transfusion requirements during liver transplant and the potential benefits to the transplanted heart to remain on cardiopulmonary bypass during liver implantation, we revised the strategy for combined heart and liver transplant. We report the clinical course of four consecutive patients who underwent this procedure in our institution. CLINICAL FEATURES: Patient 1 was a 53-yr-old male with familial hypertrophic cardiomyopathy and congestive cirrhosis. Patient 2 was a 57-yr-old male with hypertrophic restrictive cardiomyopathy and congestive cirrhosis. Patient 3 was a 48-yr-old male with dilated cardiomyopathy and hepatitis B cirrhosis. Patient 4 was a 57-yr-old male with ischemic cardiomyopathy and congestive cirrhosis. Each patient underwent combined heart and liver transplant, with liver implantation performed during cardiopulmonary bypass and anticoagulation. Estimated blood loss ranged from 1,000 to 3,000 mL. Intraoperative transfusion included 2-5 U of packed red blood cells, 4-12 U of fresh frozen plasma, 0-20 U of cryoprecipitate, and 5-23 U of platelets. All patients remain well 25-38 months after surgery. CONCLUSION: Combined heart and liver transplant during cardiopulmonary bypass is a viable strategy that may confer benefit to this unique type of patient.

Case report: nasotracheal intubation--look before leaping to assess the laryngeal view.

PURPOSE: To describe an airway management plan, including oral to nasal endotracheal tube exchange, when nasal intubation is required in the unanticipated difficult airway. CLINICAL FEATURES: A nasal intubation was required for a patient undergoing oropharyngeal surgery. Following loss of consciousness and paralysis, a Cormack-Lehane class 3 view was obtained, and pressure over the thyroid cartilage failed to reveal the vocal cords. An Eschmann bougie was inserted into the oropharynx and blindly entered the trachea. An orotracheal tube was advanced into the trachea over the bougie, and the patient was ventilated with 100% O2 following the bougie's removal. An endotracheal tube was then guided through the right nostril into the hypopharynx. An Eschmann bougie was inserted into the nasal tube, and advanced towards the glottic opening under laryngoscopic view. Digital pressure applied to the oral tube at the base of the tongue brought the vocal cords into view. The oral endotracheal cuff was deflated, and the bougie (inserted into the nasal tube) was advanced into the trachea alongside the orotracheal tube. The orotracheal tube was withdrawn, and the nasal tube was advanced into the trachea over the bougie. The patient's O2 saturation and end-tidal CO2 concentration remained at 99-100% and 30-33 mmHg, respectively, during these maneuvers, which required only a few minutes to perform. CONCLUSION: When nasotracheal intubation is required, a plan of airway management is required to safely secure the airway. We emphasize the importance of direct laryngoscopy prior to insertion of an endotracheal tube through the nose, and describe a strategy for oral to nasal tracheal tube exchange.

Nail-Patella syndrome: a case report and anesthetic implications.

PURPOSE: To report a case of asystole during combined epidural and general anesthesia occurring in a patient with Nail-Patella syndrome (NPS), and to review the management and anesthetic implications of this rare genetic syndrome. CLINICAL FEATURES: A 64-yr-old male with NPS, renal impairment and coronary artery disease presented for right hemicolectomy for colon cancer. Following initiation of surgery and during insertion of a nasogastric tube there was sudden loss of the patient's pulse oxymetry, and arterial pressure waveforms with an asystolic electrocardiogram signal. Atropine 0.6 mg i.v. was administered and after an asystolic period of 20-30 sec, myocardial activity commenced at 110 beatsxmin(-1) with return of normal vital signs and no further sequelae. CONCLUSIONS: Nail-Patella syndrome can present with an array of anomalies that may be associated with perioperative complications. Glaucoma, nephropathy, vasomotor dysfunction, fragile teeth, abnormal muscle, skeletal and nerve anatomy as well as involvement of the central and/or peripheral nervous systems are common findings. In this setting it is postulated that a vasovagal reflex from esophageal stimulation by nasogastric tube placement may have caused the asystolic event. This response could have been exaggerated by the sympatholytic combination of neuraxial block, preoperative beta-blockade, and potential autonomic dysfunction secondary to NPS. Awareness of this uncommon disease and its presentation may serve to caution the anesthesiologist regarding the perioperative implications of patients with this syndrome.

Effect of laparoscopic versus open gastric bypass surgery on postoperative pain and bowel function.

BACKGROUND: This study was designed to assess postoperative pain and bowel function in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGBP) performed either by open or laparoscopic technique. METHODS: We prospectively studied patients scheduled for RYGBP between July 2002 and June 2003. Patients were assigned to the laparoscopic or open procedure by one surgeon. All patients received patient controlled analgesia (PCA) with intravenous morphine and rectal naproxen 500 mg every 12 hours. Postoperative analgesia was assessed daily using a visual analog scale (VAS) at rest, on walking and coughing. The amount of morphine used during the first 48 hours, the time of return of gastrointestinal motility and the time until first oral food intake were recorded. RESULTS: 53 patients were enrolled and studied (laparoscopic group n=33, open group n=20). Patients undergoing laparoscopic RYGBP requested less morphine (P=0.0001) and showed lower VAS pain scores than patients undergoing open RYGBP. The return of bowel movement in the laparoscopic group occurred 1 day earlier than in the open group (P=0.01). The time to first passage of gas (P=0.01) and oral food intake (P=0.06) was shorter after laparoscopic than after open RYGBP. Patients in the laparoscopic group were discharged 1(1/2) days earlier than patients in the open group (P=0.01). CONCLUSION: The laparoscopic RYGBP operation was associated with less postoperative pain and morphine consumption than the open RYGBP, thereby facilitating an earlier recovery of intestinal motility.

Cortical processing of complex auditory stimuli during alterations of consciousness with the general anesthetic propofol.

BACKGROUND: The extent to which complex auditory stimuli are processed and differentiated during general anesthesia is unknown. The authors used blood oxygenation level-dependent functional magnetic resonance imaging to examine the processing words (10 per period; compared with scrambled words) and nonspeech human vocal sounds (10 per period; compared with environmental sounds) during propofol anesthesia. METHODS: Seven healthy subjects were tested. Propofol was given by a computer-controlled pump to obtain stable plasma concentrations. Data were acquired during awake baseline, sedation (propofol concentration in arterial plasma: 0.64 +/- 0.13 microg/ml; mean +/- SD), general anesthesia (4.62 +/- 0.57 microg/ml), and recovery. Subjects were asked to memorize the words. RESULTS: During all periods including anesthesia, the sounds conditions combined elicited significantly greater activations than silence bilaterally in primary auditory cortices (Heschl gyrus) and adjacent regions within the planum temporale. During sedation and anesthesia, however, the magnitude of the activations was reduced by 40-50% (P < 0.05). Furthermore, anesthesia abolished voice-specific activations seen bilaterally in the superior temporal sulcus during the other periods as well as word-specific activations bilaterally in the Heschl gyrus, planum temporale, and superior temporal gyrus. However, scrambled words paradoxically elicited significantly more activation than normal words bilaterally in planum temporale during anesthesia. Recognition the next day occurred only for words presented during baseline plus recovery and was correlated (P < 0.01) with activity in right and left planum temporale. CONCLUSIONS: The authors conclude that during anesthesia, the primary and association auditory cortices remain responsive to complex auditory stimuli, but in a nonspecific way such that the ability for higher-level analysis is lost.