Functional brain imaging offers a way to investigate how general anaesthetics impair consciousness. However, functional imaging changes may result from drug effects unrelated to hypnosis. ...Establishing a causal link with loss of consciousness is thus difficult.
To identify changes of neuronal activity functionally linked to the level of consciousness, physostigmine was used to restore consciousness without changing the anaesthetic concentration in 11 subjects anaesthetized with propofol. Eight subjects (responders) regained consciousness after physostigmine and three did not (non-responders). Positron emission tomography was used to measure regional cerebral blood flow (rCBF); during baseline (awake), after anaesthesia-induced loss of consciousness, after physostigmine administration, and recovery. In addition to subtraction analyses, we used conjunction analysis in the responders to identify changes common to the baseline–anaesthesia and physostigmine–anaesthesia contrasts.
Complete data were available for seven subjects (four responders and three non-responders). The analyses revealed that unconsciousness was associated with rCBF decreases in the thalamus and precuneus. Restoration of consciousness by physostigmine was associated with rCBF increases in these same structures, with the strongest effect in the thalamus.
The results provide strong evidence that reductions in rCBF in the thalamus and precuneus are functionally related to propofol-induced unconsciousness independently of any non-specific effects of propofol. These observations confirm that the thalamus and precuneus are key elements to understand how general anaesthetics cause unconsciousness and how patients wake up from anaesthesia. Furthermore, they are consistent with the notion that anaesthetic-induced unconsciousness is associated with reduced cholinergic activation.
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.
In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from ...the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes. In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures. We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.
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.
It is postulated that alteration of central cholinergic transmission plays an important role in the mechanism by which anesthetics produce unconsciousness. The authors investigated the effect of ...altering central cholinergic transmission, by physostigmine and scopolamine, on unconsciousness produced by propofol.
Propofol was administered to American Society of Anesthesiologists physical status 1 (n = 17) volunteers with use of a computer-controlled infusion pump at increasing concentrations until unconsciousness resulted (inability to respond to verbal commands, abolition of spontaneous movement). Central nervous system function was assessed by use of the Auditory Steady State Response (ASSR) and Bispectral Index (BIS) analysis of electrooculogram. During continuous administration of propofol, reversal of unconsciousness produced by physostigmine (28 microgram/kg) and block of this reversal by scopolamine (8.6 microgram/kg) were evaluated.
Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 (+/- SD) microgram/ml (n = 17). Unconsciousness was associated with reductions in ASSR (0.10 +/- 0.08 microV awake baseline 0.32 +/- 0.18 microV, P < 0.001) and BIS (55.7 +/- 8.8 awake baseline 92.4 +/- 3.9, P < 0.001). Physostigmine restored consciousness in 9 of 11 subjects, with concomitant increases in ASSR (0.38 +/- 0.17 microV, P < 0.01) and BIS (75.3 +/- 8.3, P < 0.001). In all subjects (n = 6) scopolamine blocked the physostigmine-induced reversal of unconsciousness and the increase of the ASSR and BIS (ASSR and BIS during propofol-induced unconsciousness: 0.09 +/- 0.09 microV and 58.2 +/- 7.5, respectively; ASSR and BIS after physostigmine administration: 0.08 +/- 0.06 microV and 56.8 +/- 6.7, respectively, NS).
These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.
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.
Introduction & Objectives : Antibiotic prophylaxis are administered as a routine to decrease the risk for septic complications following transrectal prostate biopsy. Fosfomycin administered 1 h ...or more prior to biopsy has equal or better infectious complication rates as compared to Ciprofloxacin in both prospective and retrospective studies from countries with high rates of antibiotic resistance. The aim of this study was to investigate if Fosfomycin administered immediately prior to prostate biopsy was as effective as Ciprofloxacin in Sweden, a country with low rates of antibiotic resistance.
Materials & Methods : A randomized, controlled, open, multicenter, non-inferiority-study including men of all ages undergoing transrectal prostate biopsy was performed in the urology departments of three Swedish hospitals. The total number of patients were planned for 3448, divided into low and high infection risk groups. The low-risk group was randomized to either one dose of Fosfomycin 3g or Ciprofloxacin 750mg before biopsy. The high-risk group was randomized to either two doses of Fosfomycin 3g prior to biopsy and one more 24 h after biopsy or Ciprofloxacin 500mg once prior to biopsy and then twice daily for three days. The drugs were administered orally. All patients had a rectal swab for culture before and after biopsy. The endpoint was hospitalisation due to urinary tract infection within 14 days from biopsy, follow-up was performed with a phone interview.
Results : The safety board prematurely interrupted the study after 42 included patients due to an unusual high number of hospitalisations. Four out of 20 patients (20%), three in the low-risk group and one in the high-risk group, had been hospitalised due to urosepsis in the Fosfomycin group. One further patient described fever symptoms but did not seek health care. No patient in the Ciprofloxacin group (n=21) described symptoms of infection from the urinary tract. One patient was lost to follow-up. A one-sided binomial test showed a p-value of <0.001. Two of the four hospitalised patients had a positive blood culture for Pseudomonas Aeruginosa and one had a positive rectal swab culture for Pseudomonas species both before and after biopsy.
Conclusions : The study does not support the use of Fosfomycin administered immediately prior to prostate biopsy. The results may have been affected by the unexpected high number of Pseudomonas infections, a bacteria where Fosfomycin often lack effect. If Fosfomycin is to be used it should be with caution if Pseudomonas has been seen in earlier cultures
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.
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.
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.
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.
The groundwater in a shallow, unconfined, low-lying coastal aquifer in Santala, southern Finland, was chemically characterised by integrating multivariate statistical approaches, principal component ...analysis (PCA) and hierarchical cluster analysis (HCA), based on the stable isotopes δ2H and δ18O, hydrogeochemistry and field monitoring data. PCA and HCA yielded similar results and classified groundwater samples into six distinct groups that revealed the factors controlling temporal and spatial variations in the groundwater geochemistry, such as the geology, anthropogenic sources from human activities, climate and surface water. High temporal variation in groundwater chemistry directly corresponded to precipitation. With an increase in precipitation, KMnO4 consumption, EC, alkalinity and Ca concentrations also increased in most wells, while Fe, Al, Mn and SO4 were occasionally increased during spring after the snowmelt under specific geological conditions. The continued increase in NO3 and metal concentrations in groundwater indicates the potential contamination risk to the aquifer. Stable isotopes of δ18O and δ2H indicate groundwater recharge directly from meteoric water, with an insignificant contribution from lake water, and no seawater intrusion into the aquifer. Groundwater geochemistry suggests that local seawater intrusion is temporarily able to take place in the sulfate reduction zone along the freshwater and seawater mixed zone in the low-lying coastal area, but the contribution of seawater was found to be very low. The influence of lake water could be observed from higher levels of KMnO4 consumption in wells near the lake. The integration of PCA and HCA with conventional classification of groundwater types, as well as with the hydrogeochemical data, provided useful tools to identify the vulnerable groundwater areas representing the impacts of both natural and human activities on water quality and the understanding of complex groundwater flow system for the aquifer vulnerability assessment and groundwater management in the future.
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