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Concept: Anesthetic


General anesthetics are used during medical and surgical procedures to reversibly induce a state of total unconsciousness in patients. Here, we investigate, from a dynamic network perspective, how the cortical and cardiovascular systems behave during anesthesia by applying nonparametric spectral techniques to cortical electroencephalography, electrocardiogram and respiratory signals recorded from anesthetized rats under two drugs, ketamine-xylazine (KX) and pentobarbital (PB). We find that the patterns of low-frequency cortico-cardio-respiratory network interactions may undergo significant changes in network activity strengths and in number of network links at different depths of anesthesia dependent upon anesthetics used.

Concepts: Pharmacology, Surgery, Anesthesia, General anaesthesia, Chloroform, Local anesthetic, Anesthetic, EEG measures during anesthesia


OBJECTIVE: To compare a towel under, a warm water pad under or a forced warm air blanket over dogs as techniques to reduce heat loss during a standardized anesthetic. STUDY DESIGN: Prospective, randomized, crossover study. ANIMALS: Eight, healthy, mixed breed dogs weighing 16.3-19.6 kg. METHODS: Dogs were anesthetized four times for 90 minutes. Dogs were placed on a steel table (treatment TA), with a cotton towel (treatment TO) or a circulating warm water pad (treatment WP) between the dog and the table, or with, a towel under the dog and covered with a forced warm air blanket (treatment WAB). Rectal temperature (RT) was recorded at 5 minute intervals. Changes in temperature (ΔRT) were calculated as the RT at a given point subtracted from the RT before anesthesia (baseline) and compared over time. RESULTS: After 90 minutes of anesthesia, the ΔRT was 3.42 °C ± 0.29 for TA, 2.78 °C ± 0.43 for TO, 1.98 °C ± 0.29 for WP, and 0.91 °C ± 0.27 for WAB. Significant differences in ΔRT occurred between TA and WAB at 20 minutes (0.94 °C ± 0.42, p = 0.0206), between TO and WAB at 30 minutes (1.16 °C ± 0.62, p = 0.0063), between WP and WAB at 50 minutes (0.96 °C ± 0.98, p = 0.0249), between TA and WP at 35 minutes (1.19 °C ± 0.54, p = 0.0091), between TO and WP at 70 minutes (1.12 °C ± 0.56, p = 0.0248), and between TA and TO at 75 minutes (0.96 °C ± 0.62, p = 0.0313). These differences in ΔRT between each treatment persisted from the times indicated until the end of the anesthesia. CONCLUSION AND CLINICAL RELEVANCE: During anesthesia, forced warm air blankets were superior to other methods tested for limiting heat loss. An efficient heat loss technique should be used for anesthesia longer than 20 minutes duration in medium sized dogs.

Concepts: Crossover study, Thermodynamics, Heat, Anesthesia, Selective breeding, Dog breed, Anesthetic, Mixed-breed dog


The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants.

Concepts: Randomized controlled trial, Anesthesia, Local anesthesia, Morphine, Ketamine, Local anesthetic, Anesthetic, Nerve block


The neurophysiological mechanisms by which anesthetic drugs cause loss of consciousness are poorly understood. Anesthetic actions at the molecular, cellular, and systems levels have been studied in detail at steady states of deep general anesthesia. However, little is known about how anesthetics alter neural activity during the transition into unconsciousness. We recorded simultaneous multiscale neural activity from human cortex, including ensembles of single neurons, local field potentials, and intracranial electrocorticograms, during induction of general anesthesia. We analyzed local and global neuronal network changes that occurred simultaneously with loss of consciousness. We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (<1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space. Local (<4 mm) neuronal populations maintain the millisecond-scale connectivity patterns observed in the awake state, and spike rates fluctuate and can reach baseline levels. However, neuronal spiking occurs only within a limited slow oscillation-phase window and is silent otherwise, fragmenting the time course of neural activity. Unexpectedly, we found that these slow oscillations occur asynchronously across cortex, disrupting functional connectivity between cortical areas. We conclude that the onset of slow oscillations is a neural correlate of propofol-induced loss of consciousness, marking a shift to cortical dynamics in which local neuronal networks remain intact but become functionally isolated in time and space.

Concepts: Nervous system, Neuron, Brain, Cognition, Cerebral cortex, Anesthesia, Local anesthetic, Anesthetic


BACKGROUND:Between 1992 and 2011, 373 Canadian individuals with adverse anesthetic reaction were referred to the Malignant Hyperthermia Unit in Toronto, Ontario, Canada for malignant hyperthermia (MH) diagnostic testing. We analyzed the epidemiologic characteristics of the index adverse anesthetics for those probands who were confirmed to be MH susceptible.METHODS:One hundred twenty-nine proband survivors of adverse anesthetic reactions, whose MH susceptible status was confirmed by caffeine-halothane contracture testing were selected. Individuals were excluded if the index anesthetic record was not available for review. Data regarding demographics, clinical signs, laboratory findings, treatment, and complications were retrospectively compiled and analyzed. A Fisher exact test and χ(2) test were applied to compare categorical variables. The Wilcoxon rank-sum test was applied with continuous variables.RESULTS:Young males (61.2%) dominated among selected patients. Seventeen of 129 (13.2%) patients had prior unremarkable anesthesia. Anesthetic triggers were volatile-only (n = 58), succinylcholine-only (n = 20), or both volatile and succinylcholine (n = 51). Eight (6.2%) cases occurred in the postanesthetic care unit. There were no reactions after discharge from the postanesthetic care unit. The most frequent clinical signs were hyperthermia (66.7%), sinus tachycardia (62.0%), and hypercarbia (51.9%). Complications occurred in 20.1% of patients, the most common complication being renal dysfunction. When 20 or more minutes between the first adverse sign and dantrolene treatment elapsed, complication rates increased to ≥30%.CONCLUSIONS:This is the first Canadian study in 3 decades to report nationwide data on MH epidemiology. Features that differ from earlier reports include a 15.5% incidence of reactions triggered by succinylcholine alone and lower complication rates. In agreement with previously published studies, we confirmed in this independent dataset that increased complication rates were associated with an increased time interval between the first adverse clinical sign and dantrolene treatment. This underscores the need for early diagnosis and rapid dantrolene access and administration in anesthetizing locations using either succinylcholine or volatile anesthetic drugs.

Concepts: Statistical tests, Anesthesia, Malignant hyperthermia, Fever, Ketamine, Local anesthetic, Anesthetic, Anesthetics


Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction is an increasingly common diagnosis in patients who are being seen at tertiary care children’s hospitals. We present two cases of anesthetics from the authors' own experience in addition to a comprehensive review of the disorder and anesthetic implications.

Concepts: Hospital, Physician, Anesthesia, Morphine, Ketamine, Anesthetic, ROHHAD, Anesthetics


We hypothesize that isoflurane and ketamine impact ventilatory pattern variability (VPV) differently. Adult Sprague-Dawley rats were recorded in a whole-body plethysmograph before, during and after deep anesthesia. VPV was quantified from 60-s epochs using a complementary set of analytic techniques that included constructing surrogate data sets that preserved the linear structure but disrupted nonlinear deterministic properties of the original data. Even though isoflurane decreased and ketamine increased respiratory rate, VPV as quantified by the coefficient of variation decreased for both anesthetics. Further, mutual information increased and sample entropy decreased and the nonlinear complexity index (NLCI) increased during anesthesia despite qualitative differences in the shape and period of the waveform. Surprisingly mutual information and sample entropy did not change in the surrogate sets constructed from isoflurane data, but in those constructed from ketamine data, mutual information increased and sample entropy decreased significantly in the surrogate segments constructed from anesthetized relative to unanesthetized epochs. These data suggest that separate mechanisms modulate linear and nonlinear variability of breathing.

Concepts: Fundamental physics concepts, Anesthesia, Randomness, Surrogate, Information theory, Ketamine, Local anesthetic, Anesthetic


OBJECTIVE: To describe the prevalence of dysphoria after intraoperative administration of fentanyl by infusion and identify other risk factors influencing this in dogs undergoing stifle surgery. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Dogs (n = 92) that had tibial plateau leveling osteotomy (TPLO) or tibial tuberosity advancement (TTA). METHODS: Dogs were anesthetized using a standardized anesthetic protocol, and randomly assigned to receive a loading dose followed by 1 of 3 infusions of fentanyl perioperatively: 2 μg/kg/h, 10 μg/kg/h, or 20 μg/kg/h. Dog characteristics and all additional medications were recorded and included as part of the statistical analysis. Dog behavior was scored before anesthesia and during recovery using a scale of 1-4 (Appendices A and B). If no improvement in behavior was seen in 3-5 minutes postextubation, dogs with a score of 3 or 4 during recovery were administered fentanyl (2 μg/kg intravenously [IV]) in the event that the behaviors associated with the higher scores were related to pain. If they did not respond favorably to the administration of additional fentanyl and wound palpation did not elicit a response, but the untoward behaviors continued, dogs were administered either a tranquilizer, sedative, or opioid antagonist, and were considered dysphoric. RESULTS: Of 92 dogs, 22 (23.9%) were considered dysphoric using aforementioned criteria. CONCLUSIONS: About one-fourth of dogs enrolled in this study were dysphoric based on study criteria.

Concepts: Pharmacology, Epidemiology, Medical statistics, The Canon of Medicine, Anesthesia, Opioid, Dog, Anesthetic


Objective monitoring of the level of anesthesia is crucial in carefully controlled translational neuroscience studies. The usefulness of bispectral index (BIS) in monitoring human anesthesia is well established. However, the validity of its application remains unproven in laboratory animals. We assessed whether BIS could be used reliably in monitoring the depth of deep anesthesia in 8 New Zealand white rabbits. Experimental baseline anesthesia was maintained with continuous infusion of propofol and administration of isoflurane, both of which were titrated to EEG activity. The rabbits were allocated randomly to receive 3 increasing concentrations of common anesthetic drugs (etomidate, propofol, and isoflurane) aimed to produce burst suppression of EEG activity yielding at least 10 s of sustained EEG silence. Rabbits had a 20-min recovery interval between challenges. Transient cerebral hypoperfusion to produce reversible EEG silence due to ischemia was induced as a fourth challenge, followed by terminal arrest, in each animal. BIS, EEG, and physiologic data were analyzed for each rabbit. We observed stable BIS values in the range of 40 to 60 during the administration of baseline anesthesia. However, as the depth of anesthesia deepened with the anesthetic drug challenges, the BIS value paradoxically increased with increasing doses. The BIS signal quality index declined while the total power decreased. In contrast to these unexpected results, BIS values decreased rapidly to near 0 during terminal arrest, as expected. Therefore, we do not consider BIS to be a useful method for monitoring deep levels of anesthesia in laboratory rabbits.

Concepts: Neuroscience, Economics, Electroencephalography, Anesthesia, Ketamine, Local anesthetic, Rabbit, Anesthetic


Objective-To evaluate the efficacy and safety of a combination of dexmedetomidine, butorphanol, and midazolam administered IM for anesthesia in captive Asian small-clawed otters (Aonyx cinereus) and to compare this combination with a combination of ketamine and midazolam. Design-Prospective crossover study. Animals-10 captive Asian small-clawed otters. Procedures-A combination of either dexmedetomidine (0.03 mg/kg [0.014 mg/lb]), butorphanol (0.2 mg/kg [0.091 mg/lb]), and midazolam (0.15 mg/kg [0.068 mg/lb]) or ketamine (10.1 mg/kg [4.59 mg/lb]) and midazolam (0.3 mg/kg [0.14 mg/lb]) was administered IM to otters for immobilization to allow scheduled wellness examinations. Otters were intubated and administered 100% oxygen during the examination. Anesthesia was supplemented with isoflurane in oxygen if necessary. Routine medical procedures, including blood collection, radiography, echocardiography, dental scaling, vaccinations, and contraception administration, were performed as indicated during the immobilization. Physiologic, clinicopathologic, and anesthetic variables were recorded and compared. Otters given dexmedetomidine-butorphanol-midazolam were administered atipamezole (0.2 mg/kg [0.091 mg/lb]), naltrexone (0.6 mg/kg [0.27 mg/lb]), and flumazenil (0.05 mg/kg [0.023 mg/lb]) IM at the completion of the examination. Results-The need for and duration of isoflurane administration were greater for ketamine-midazolam anesthesia, compared with dexmedetomidine-butorphanol-midazolam anesthesia. Recoveries were shorter and subjectively smoother with dexmedetomidine-butorphanol-midazolam. Heart rates were significantly higher during ketamine-midazolam anesthesia. Regardless of protocol, all otters developed hypothermia and hypercapnia during anesthesia. Conclusions and Clinical Relevance-Both protocols were safe and effective for this species, but the reversible nature of dexmedetomidine-butorphanol-midazolam resulted in more rapid recoveries than did ketamine-midazolam. Otters anesthetized with ketamine-midazolam may require additional anesthetic medications for routine examinations, and assisted ventilation and thermal support may be of benefit with either protocol.

Concepts: Anesthesia, Opioid, Otters, Anesthetic, Mammals of Asia, Aonyx, Oriental Small-clawed Otter