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1.  Bispectral Index Monitor 
Executive Summary
The objective of this analysis was to evaluate the effectiveness and cost-effectiveness of the bispectral index (BIS) monitor, a commercial device to assess the depth of anesthesia.
Conventional methods to assess depth of consciousness, such as cardiovascular and pulmonary measures (e.g., heart rate, systolic/diastolic blood pressure, mean arterial pressure, respiratory rate, and level of oxygen in the blood), and clinical signs (e.g., perspiration, shedding of tears, and limb movement) are not reliable methods to evaluate the brain status of anesthetized patients. Recent progress in understanding the electrophysiology of the brain has led to the development of cerebral monitoring devices that identify changes in electrophysiologic brain activity during general anesthesia. The BIS monitor, derived from electroencephalogram (EEG) data, has been used as a statistical predictor of the level of hypnosis and has been proposed as a tool to reduce the risk of intraoperative awareness.
Anesthesia that is too light can result in the recall of events or conversations that happen in the operation room. Patients have recalled explicit details of conversations that happened while under anesthesia. This awareness is frightening for patients and can lead to post-traumatic stress disorder. Conversely, anesthesia that is too deep can cause hemodynamic disturbances necessitating the use of vasoconstrictor agents, which constrict blood vessels, to maintain normal blood pressure and cardiac output. Overly deep anesthesia can also result in respiratory depression requiring respiratory assistance postoperatively.
Monitoring the depth of anaesthesia should prevent intraoperative awareness and help to ensure that an exact dose of anaesthetic drugs is given to minimize adverse cardiovascular effects caused by overly large doses. Researchers have suggested that cerebral monitoring can be used to assess the depth of anesthesia, prevent awareness, and speed early recovery after general anesthesia by optimizing drug delivery to each patient.
Awareness is a rare complication in general anesthesia. The risk of intraoperative awareness varies among countries, depending on their anesthetic practices. In the United States, the incidence of intraoperative awareness is 0.1% to 0.2% of patients undergoing general anesthesia. The incidence of intraoperative awareness depends on the type of surgery. Trauma patients have reported the highest incidence of intraoperative awareness (11%–43%) followed by patients undergoing cardiac surgery (1.14%) and patients undergoing Cesarean section (0.9%).
The BIS monitor, licensed by Health Canada, is the first quantitative EEG index used in clinical practice as a monitor to assess the depth of anesthesia. It consists of a sensor, a digital signal converter, and a monitor. The sensor is placed on the patient’s forehead to pick up the electrical signals from the cerebral cortex and transfer them to the digital signal converter. A BIS score quantifies changes in the electrophysiologic state of the brain during anesthesia. In patients who are awake, a typical BIS score is 90 to 100. Complete suppression of cortical activity results in a BIS score of 0, known as a flat line. Lower numbers indicate a higher hypnotic effect. Overall, a BIS value below 60 is associated with a low probability of response to commands. There are several alternative technologies to quantify the depth of anesthesia, but only the BIS and SNAP monitors are licensed in Canada. The list price of the BIS monitor is $13,500 (Cdn). The sensors cost $773 (Cdn) for a box of 25.
Because intraoperative awareness and recall happen rarely, only 1 randomized controlled trial of all the studies reviewed, was adequately powered to show the impact of BIS monitoring. This was a large prospective, randomized, double-blinded, multicentre study that was designed to investigate if BIS-guided anesthesia reduces the incidence of intraoperative awareness. The study confirmed 2 cases of intraoperative awareness in the BIS group and 11 cases in the standard practice group. This difference was statistically significant (P =.022). There were 36 reports of possible awareness that were not confirmed by the study group (20 patients in the BIS group and 16 in the standard practice group).
Additionally, the results of small randomized controlled trials and prospective cohort studies show that, overall, BIS monitoring is relatively good at indicating the state of being alert; however, its algorithm does not accurately predict an unconscious state. BIS monitoring has low sensitivity for the detection of the state of being asleep, and it may show values higher than 60 in those already asleep. Therefore, an unknown percentage of patients will not be identified as being asleep and will receive anesthetics unnecessarily.
Based on the literature review, the Medical Advisory Secretariat concludes the following:
Prevention of awareness should remain a clinical decision for anesthesiologists to make based on their experience with intraoperative awareness in their practices.
Although BIS monitoring may have a positive impact on reducing the incidence of intraoperative awareness in the general population, its negative impact on individual patients may overshadow this positive outcome.
BIS monitoring is good at indicating an “alert” state, which is why it can reduce the incidence of intraoperative awareness; however, its algorithm does not accurately predict an “asleep” state. This means an unknown percentage of patients who are already asleep will not be identified because of falsely elevated BIS values. These patients will receive unnecessary dosage of anesthetics resulting in a deep hypnotic state.
Adherence to the practice guidelines will reduce the risk of intraoperative awareness.
PMCID: PMC3387745  PMID: 23074459
2.  The influence of various anesthesia techniques on postoperative recovery and discharge criteria among geriatric patients 
Clinics  2010;65(10):941-946.
We aim to compare selective spinal anesthesia and general anesthesia with regard to postoperative recovery and fast‐track eligibility in day surgeries.
Sixty geriatric outpatient cases, with ASA II‐III physical status and requiring short‐duration transurethral intervention, were enrolled in the study. The cases were split into 2 groups: as general anesthesia (Group GA) and selective spinal anesthesia (Group SSA). Group GA (n = 30) received propofol 2 mg kg‐1 (until loss of eyelash reflex), remifentanil induction 0.5‐1 µg kg‐1, and laryngeal mask. Maintenance was achieved by 4‐6% desflurane in 60% N2O and 40% O2 along with remifentanil infusion at 0.05 µg /kg‐1 /min‐1. Drugs were discontinued after the withdrawal of the ureteroscope, and extubation was carried out with 100% O2. Group SSA (n = 30) received 0.5% spinal anesthesia via L4‐5 space by 0.5% hyperbaric bupivacaine 5 mg. Anesthesia preparation time, time to surgical anesthesia level, postoperative fast‐tracking, and time to White‐Song recovery score of 12, were noted. In the operating room, we evaluated hemodynamics, nausea/vomiting, surgeon and patient satisfaction with anesthesia, perioperative midazolam‐fentanyl administration, postoperative pain, and discharge time.
Anesthesia preparation time, length of surgery, anesthesia‐related time in the operating room, time to sit, and time to walk were significantly low in Group GA (p<0.05), whereas time to fast‐track eligibility, length of stay in the PACU, discharge time, and other parameters were similar in both of the groups.
While anesthesia preparation time, length of surgery, start time of surgery, time to sit, and time to walk were shorter in the General Anesthesia group, time to fast‐track eligibility, phase 1 recovery time, and discharge time were similar among patients subjected to selective spinal anesthesia.
PMCID: PMC2972597  PMID: 21120291
Selective spinal anesthesia; General anesthesia; Postoperative recovery; Fast‐track; Geriatri
3.  Comparison of alphabetical versus categorical display format for medication order entry in a simulated touch screen anesthesia information management system: an experiment in clinician-computer interaction in anesthesia 
Anesthesia information management system (AIMS) records should be designed and configured to facilitate the accurate and prompt recording of multiple drugs administered coincidentally or in rapid succession.
We proposed two touch-screen display formats for use with our department’s new EPIC touch-screen AIMS. In one format, medication “buttons” were arranged in alphabetical order (i.e. A-C, D-H etc.). In the other, buttons were arranged in categories (Common, Fluids, Cardiovascular, Coagulation etc.). Both formats were modeled on an iPad screen to resemble the AIMS interface. Anesthesia residents, anesthesiologists, and Certified Registered Nurse Anesthetists (n = 60) were then asked to find and touch the correct buttons for a series of medications whose names were displayed to the side of the entry screen. The number of entries made within 2 minutes was recorded. This was done 3 times for each format, with the 1st format chosen randomly. Data were analyzed from the third trials with each format to minimize differences in learning.
The categorical format had a mean of 5.6 more drugs entered using the categorical method in two minutes than the alphabetical format (95% confidence interval [CI] 4.5 to 6.8, P < 0.0001). The findings were the same regardless of the order of testing (i.e. alphabetical-categorical vs. categorical - alphabetical) and participants’ years of clinical experience. Most anesthesia providers made no (0) errors for most trials (N = 96/120 trials, lower 95% limit 73%, P < 0.0001). There was no difference in error rates between the two formats (P = 0.53).
The use of touch-screen user interfaces in healthcare is increasingly common. Arrangement of drugs names in a categorical display format in the medication order-entry touch screen of an AIMS can result in faster data entry compared to an alphabetical arrangement of drugs. Results of this quality improvement project were used in our department’s design of our final intraoperative electronic anesthesia record. This testing approach using cognitive and usability engineering methods can be used to objectively design and evaluate many aspects of the clinician-computer interaction in electronic health records.
PMCID: PMC3461477  PMID: 22643058
4.  EEG slow-wave coherence changes in propofol-induced general anesthesia: experiment and theory 
The electroencephalogram (EEG) patterns recorded during general anesthetic-induced coma are closely similar to those seen during slow-wave sleep, the deepest stage of natural sleep; both states show patterns dominated by large amplitude slow waves. Slow oscillations are believed to be important for memory consolidation during natural sleep. Tracking the emergence of slow-wave oscillations during transition to unconsciousness may help us to identify drug-induced alterations of the underlying brain state, and provide insight into the mechanisms of general anesthesia. Although cellular-based mechanisms have been proposed, the origin of the slow oscillation has not yet been unambiguously established. A recent theoretical study by Steyn-Ross et al. (2013) proposes that the slow oscillation is a network, rather than cellular phenomenon. Modeling anesthesia as a moderate reduction in gap-junction interneuronal coupling, they predict an unconscious state signposted by emergent low-frequency oscillations with chaotic dynamics in space and time. They suggest that anesthetic slow-waves arise from a competitive interaction between symmetry-breaking instabilities in space (Turing) and time (Hopf), modulated by gap-junction coupling strength. A significant prediction of their model is that EEG phase coherence will decrease as the cortex transits from Turing–Hopf balance (wake) to Hopf-dominated chaotic slow-waves (unconsciousness). Here, we investigate changes in phase coherence during induction of general anesthesia. After examining 128-channel EEG traces recorded from five volunteers undergoing propofol anesthesia, we report a significant drop in sub-delta band (0.05–1.5 Hz) slow-wave coherence between frontal, occipital, and frontal–occipital electrode pairs, with the most pronounced wake-vs.-unconscious coherence changes occurring at the frontal cortex.
PMCID: PMC4212622  PMID: 25400558
slow-wave sleep; phase-coherence measure; mean-field cortical model; gap-junction; Turing–Hopf instabilities
5.  Anesthesia for Patients With Liver Disease 
Hepatitis Monthly  2014;14(7):e19881.
Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction.
Evidence Acquisition:
We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013.
Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isoflurane, Desflurane or Sevoflurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs.
Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient’s condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above mentioned rules a safe anesthesia could be achievable in these patients.
PMCID: PMC4080095  PMID: 25031586
Liver Disease; Anesthesia; Regional Anesthesia; Epidural Anesthesia; Spinal Anesthesia
6.  Leaving More Than Your Fingerprint on the Intravenous Line: A Prospective Study on Propofol Anesthesia and Implications of Stopcock Contamination 
Anesthesia and analgesia  2013;10.1213/ANE.0b013e318292ed45.
Acute care handling of IV stopcocks during anesthesia and surgery may result in contaminated IV tubing sets. In the context of widespread propofol use, a nutrient-rich hypnotic drug, we hypothesized that propofol anesthesia increases bacterial contamination of IV stopcocks and may compromise safety of IV tubing sets when continued to be used after propofol anesthesia.
We conducted an in vitro trial by collecting IV tubing sets at the time of patient discharge from same-day ambulatory procedures performed with and without propofol anesthesia. These extension sets were then held at room temperature for 6, 24, or 48 hours. We cultured 50 samples at each interval for both cohorts. Quantitative cultures were done by aspirating the IV stopcock dead space and plating the aspirate on blood agar for colony count and speciation.
Positive bacterial counts were recovered from 17.3% of propofol anesthesia stopcocks (26/150) and 18.6% of non-propofol stopcocks (28/150). At 6 hours, the average bacterial counts from stopcocks with visible residual propofol was 44 colony forming units (CFU)/mL, compared to 41 CFU/mL with no visible residual propofol and 37 CFU/mL in non-propofol anesthesia stopcocks. There was a 100-fold increase in bacterial number in contaminated stopcock dead spaces at 48 hours after propofol anesthesia. This difference remained significant when comparing positive counts from stopcocks with no visible residual propofol and non-propofol anesthesia (p-value=0.034).
There is a covert incidence and degree of IV stopcock bacterial contamination during anesthesia which is aggravated by propofol anesthetic. Propofol anesthesia may increase risk for postoperative infection because of bacterial growth in IV stopcock dead spaces.
PMCID: PMC3833883  PMID: 23749446
7.  Drugs Used for Parenteral Sedation in Dental Practice 
Anesthesia Progress  1988;35(5):199-205.
The relative efficacy and safety of drugs and combinations used clinically in dentistry as premedicants to alleviate patient apprehension are largely unsubstantiated. To evaluate the efficacy and safety of agents used for parenteral sedation through controlled clinical trials, it is first necessary to identify which drugs, doses, and routes of administration are actually used in practice. A survey instrument was developed to characterize the drugs used clinically for anesthesia and sedation by dentists with advanced training in pain control. A random sample of 500 dentists who frequently use anesthesia and sedation in practice was selected from the Fellows of the American Dental Society of Anesthesiology. The first mailing was followed by a second mailing to nonrespondents after 30 days. The respondents report a variety of parenteral sedation techniques in combination with local anesthesia (the response categories are not mutually exclusive): nitrous oxide (64%), intravenous conscious sedation (59%), intravenous “deep” sedation (47%), and outpatient general anesthesia (27%). Drugs most commonly reported for intravenous sedation include diazepam, methohexital, midazolam, and combinations of these drugs with narcotics. A total of 82 distinct drugs and combinations was reported for intravenous sedation and anesthesia. Oral premedication and intramuscular sedation are rarely used by this group. Most general anesthesia reported is done on an outpatient basis in private practice. These results indicate that a wide variety of drugs is employed for parenteral sedation in dental practice, but the most common practice among dentists with advanced training in anesthesia is local anesthesia supplemented with intravenous sedation consisting of a benzodiazepine and an opioid or a barbiturate.
PMCID: PMC2167868  PMID: 3250279
8.  Estimation of pharmacokinetic model parameters. 
This paper addresses the problem of estimating the depth of anesthesia in clinical practice where many drugs are used in combination. The aim of the project is to use pharmacokinetically-derived data to predict episodes of light anesthesia. The weighted linear combination of anesthetic drug concentrations was computed using a stochastic pharmacokinetic model. The clinical definition of light anesthesia was based on the hemodynamic consequences of autonomic nervous system responses to surgical stimuli. A rule-based expert system was used to review anesthesia records to determine instances of light anesthesia using hemodynamic criteria. It was assumed that light anesthesia was a direct consequence of the weighted linear combination of drug concentrations in the patient's body that decreased below a certain threshold. We augmented traditional two-compartment models with a stochastic component of anesthetics' concentrations to compensate for interpatient pharmacokinetic and pharmacodynamic variability. A cohort of 532 clinical anesthesia cases was examined and parameters of two compartment pharmacokinetic models for 6 intravenously administered anesthetic drugs (fentanyl, thiopenthal, morphine, propofol, midazolam, ketamine) were estimated, as well as the parameters for 2 inhalational anesthetics (N2O and isoflurane). These parameters were then prospectively applied to 22 cases that were not used for parameter estimation, and the predictive ability of the pharmacokinetic model was determined. The goal of the study is the development of a pharmacokinetic model that will be useful in predicting light anesthesia in the clinically relevant circumstance where many drugs are used concurrently.
PMCID: PMC2579053  PMID: 8563327
9.  Mortality in Anesthesia: A Systematic Review 
Clinics (Sao Paulo, Brazil)  2009;64(10):999-1006.
This systematic review of the Brazilian and worldwide literature aims to evaluate the incidence and causes of perioperative and anesthesia-related mortality. Studies were identified by searching the Medline and Scielo databases, followed by a manual search for relevant articles. Our review includes studies published between 1954 and 2007. Each publication was reviewed to identify author(s), study period, data source, perioperative mortality rates, and anesthesia-related mortality rates. Thirty-three trials were assessed. Brazilian and worldwide studies demonstrated a similar decline in anesthesia-related mortality rates, which amounted to fewer than 1 death per 10,000 anesthetics in the past two decades. Perioperative mortality rates also decreased during this period, with fewer than 20 deaths per 10,000 anesthetics in developed countries. Brazilian studies showed higher perioperative mortality rates, from 19 to 51 deaths per 10,000 anesthetics. The majority of perioperative deaths occurred in neonates, children under one year, elderly patients, males, patients of ASA III physical status or poorer, emergency surgeries, during general anesthesia, and cardiac surgery followed by thoracic, vascular, gastroenterologic, pediatric and orthopedic surgeries. The main causes of anesthesia-related mortality were problems with airway management and cardiocirculatory events related to anesthesia and drug administration. Our systematic review of the literature shows that perioperative mortality rates are higher in Brazil than in developed countries, while anesthesia-related mortality rates are similar in Brazil and in developed countries. Most cases of anesthesia-related mortality are associated with cardiocirculatory and airway events. These data may be useful in developing strategies to prevent anesthesia-related deaths.
PMCID: PMC2763076  PMID: 19841708
Anesthesia; Cardiac Arrest; Mortality; Perioperative; Review
10.  Anesthesia for Cesarean Delivery and Learning Disabilities in a Population-Based Birth Cohort 
Anesthesiology  2009;111(2):302-310.
Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort.
The educational and medical records of all children born to mothers residing in five townships of Olmsted County, MN from 1976-1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia).
Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia N=193, and regional anesthesia N=304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia prior to age 4, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P=0.017 for comparison of CD under regional anesthesia compared to vaginal delivery).
Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.
PMCID: PMC3076711  PMID: 19602960
11.  General anesthesia as a possible GABAergic modulator affects visual processing in children 
Gamma-Aminobutyric Acid (GABA) inhibitory interneurons play an important role in visual processing, as is revealed by studies administering drugs in human and monkey adults. Investigating this process in children requires different methodologies, due to ethical considerations. The current study aimed to investigate whether a new method, being general anesthesia using Sevoflurane, can be used to trace the effects of GABAergic modulation on visual brain functioning in children. To this aim, visual processing was investigated in children aged 4–12 years who were scheduled for minor urologic procedures under general anesthesia in day-care treatment. In a visual segmentation task, the difference in Event-Related Potential (ERP) response to homogeneous and textured stimuli was investigated. In addition, psychophysical performance on visual acuity and contrast sensitivity were measured. Results were compared between before and shortly after anesthesia. In two additional studies, effects at 1 day after anesthesia and possible effects of task-repetition were investigated. ERP results showed longer latency and lower amplitude of the Texture Negativity (TN) component shortly after compared to before anesthesia. No effects of anesthesia on psychophysical measurements were found. No effects at 1 day after anesthesia or of repetition were revealed either. These results show that GABAergic modulation through general anesthesia affects ERP reflections of visual segmentation in a similar way in children as benzodiazepine does in adults, but that effects are not permanent. This demonstrates that ERP measurement after anesthesia is a successful method to study effects of GABAergic modulation in children.
PMCID: PMC3632787  PMID: 23630461
GABA; development; general anesthesia; EEG; psychophysics; vision; segmentation
12.  Convulsions during cataract surgery under peribulbar anesthesia: a case report 
Locoregional anesthesia techniques are increasingly used for cataract surgery. From these techniques, peribulbar anesthesia has been very successful over the retrobulbar anesthesia seen its effectiveness and safety. However, peribulbar anesthesia is not without risk.
Case presentation
A 70-year-old African man was scheduled for cataract surgery and lens implant for his right eye. His medical history included hypertension, diabetes mellitus and gall bladder surgery. There were no personal or family antecedents of allergy, epilepsy or taking food or toxic drug. No abnormalities were detected in his preoperative evaluation. In the operating room, standard monitoring was installed and a peripheral venous catheter 18g was inserted. Peribulbar anesthesia was realized with two injections in primary gaze position. The anesthetic mixture contained lidocaine 2% and bupivacaine 0.5%. The needle used was 25GA, 19mm, ¾ inch. The first injection was performed in his lower temporal peribulbar space with 5mL of mixture; the second injection was performed with 3mL of mixture in his upper nasal peribulbar space. These injections were performed after a negative aspiration test and followed by manual compression of his globe for 5 minutes. Five minutes after peribulbar anesthesia, his blood pressure increased to 209/115mmHg requiring three bolus of nicardipine (3.0mg) to reduce his blood pressure to 134/56mmHg. One minute after, he had generalized tonic–clonic seizures. Tracheal intubation was performed. His capillary blood glucose was 170mg/dL, axillary temperature was 36.5°C, and his serum electrolytes were normal. He recovered spontaneous ventilation 1.5 hours later. A neurological examination noted no deficit. Extubation was performed 15 minutes later without incident. A brain computed tomography and electroencephalogram were unremarkable. He was discharged on the second day and operated on 1 month later under general anesthesia.
Various serious complications can occur during locoregional anesthesia techniques in ophthalmic surgery. The mastering and perfecting of these techniques by practitioners and compliance with safety standards in anesthesia are the only way to guarantee the prevention of such complications.
PMCID: PMC4088311  PMID: 24957659
Brainstem anesthesia; Cataract surgery; Convulsions; Peribulbar anesthesia
13.  Perioperative effects of various anesthetic adjuvants with TIVA guided by bispectral index 
Korean Journal of Anesthesiology  2012;63(2):113-119.
This prospective, randomized, double blinded, controlled study was designed to compare effects of intravenous co-administration of clonidine, magnesium, or ketamine on anesthetic consumption, intraoperative hemodynamics, postoperative analgesia and recovery indices during Bispectral Index (BIS) guided total intravenous anesthesia (TIVA).
After ethical committee approval and written informed consent, 120 adult patients ASA I and II scheduled for open cholecystectomy were randomly assigned to one of 4 equal groups. Group CL received clonidine 3 µg/kg and maintained by 2 µg/kg/h. Group MG received magnesium sulphate 50 mg/kg and maintained by 8 mg/kg/h. Group KET received racemic ketamine 0.4 mg/kg and maintained by 0.2 mg/kg/h. Control group (CT) received the same volume of isotonic saline. Anesthesia was induced and maintained by fentanyl, propofol and rocuronium. Propofol infusion was adjusted to keep the BIS value between 45-55. Intraoperative hemodynamics, induction time, anesthetic consumption, recovery indices, and PACU discharge were recorded.
Induction time, propofol requirements for induction and maintenance of anesthesia, intraoperative fentanyl and hemodynamic values were significantly lower with Groups CL and MG compared to Groups KET and CT (P < 0.05). Patients in Group MG showed significantly lower muscle relaxant consumption, delayed recovery and PACU discharge than other groups (P < 0.05). First, analgesic requirement was significantly longer and total postoperative analgesic consumption was significantly lower in the adjuvant groups versus Group CT (P < 0.05).
Clonidine, magnesium, and ketamine can be useful adjuvant agents to BIS-guided TIVA. Pharmacokinetic studies of such drug combinations were recommended to investigate their interaction.
PMCID: PMC3427802  PMID: 22949977
BIS; Clonidine; Ketamine; Magnesium; TIVA
14.  General anesthesia for disabled patients in dental practice. 
Anesthesia Progress  1998;45(4):134-138.
We reviewed the cases of 91 consecutive patients with disabilities who required general anesthesia at a tertiary referral center for dental treatment with a view to determining the factors that create difficulties in the anesthetic management. The more important of these are the special difficulties involved in making preoperative assessments of these patients and the difficulty in establishing monitoring. Other difficulties in anesthesia for these patients involve problems with gaining intravenous access, problems in determining when there has been adequate recovery from anesthesia, and problems in determining the degree of discomfort or pain the patients experience after dental treatment. Another potential hazard in this group of patients is the risk of drug interactions. We emphasize the need to train anesthetists in the care of disabled patients.
PMCID: PMC2148978  PMID: 10483384
15.  Increased Anesthesia Time Using 2,2,2-tribromoethanol-Chloral Hydrate With Low Impact On Mouse Psychoacoustics 
Journal of neuroscience methods  2013;219(1):10.1016/j.jneumeth.2013.07.004.
To examine psychoacoustics in mice, we have used 2,2,2-tribromoethanol anesthesia in multiple studies. We find this drug is fast-acting and yields consistent results, providing 30 – 40 min of anesthesia. Our recent studies in binaural hearing prompted development of a regimen to anesthesia time to one hour. We tested a novel cocktail using 2,2,2-tribromoethanol coupled with low dose chloral hydrate to extend the effective anesthesia time.
New Method
We have established an intraperitoneal dosing regimen for 2,2,2-tribromoethanol-chloral hydrate anesthesia. To measure efficacy of the drug cocktail, we measured auditory brainstem responses (ABRs) at 10 min intervals to determine the effects on hearing thresholds and wave amplitudes and latencies.
This novel drug combination increases effective anesthesia to one hour. ABR Wave I amplitudes, but not latencies, are marginally suppressed. Additionally, amplitudes of the centrally-derived Waves III and V show significant inter-animal variability that is independent of stimulus intensity. These data argue against the systematic suppression of ABRs by the drug cocktail.
Comparison with Existing Methods
Using 2,2,2-tribromoethanol-chloral hydrate combination in psychoacoustic studies has several advantages over other drug cocktails, the most important being preservation of latencies from centrally- and peripherally-derived ABR waves. In addition, hearing thresholds are unchanged and wave amplitudes are not systematically suppressed, although they exhibit greater variability.
We demonstrate that 375 mg/kg 2,2,2-tribromoethanol followed after five min by 200 mg/kg chloral hydrate provides an anesthesia time of 60 min, has negligible effects on ABR wave latencies and thresholds and non-systematic effects on amplitudes.
PMCID: PMC3818901  PMID: 23856212
2,2,2-tribromoethanol; Amplitude; Auditory evoked potential; Avertin; Chloral hydrate; Electrophysiology; Latency; Neurophysiology; Psychoacoustics
16.  The Effect of Epidural Bupivacaine on BIS Levels in the Awake Phase and on the Maintenance Doses of Propofol and Fentanyl During General Anesthesia 
Anesthesiology and Pain Medicine  2013;2(4):149-153.
Simultaneous administration of epidural local anesthetic agents (LA) and general anesthetics (intravenous or inhaled) is a common procedure in patients undergoing major operations. The effects of epidural anesthesia during combined general-epidural anesthesia on the alertness level (CGEA) in the awake phase and the doses of anesthetics have been reported.
The present study was designed to determine the effects of epidural bupivacaine on the alertness level measured by bispectral index (BIS) in the awake phase and the maintenance doses of propofol and fentanyl during general anesthesia for vascular operation on the lower limb.
Patients and Methods
A double-blinded randomized clinical trial was conducted on patients awaiting vascular surgery on lower extremities in a teaching hospital from October 2007 to October 2008. During the epidural anesthesia, the control group received 0.9% NS while 0.125% bupivacaine was injected in the case group via the epidural route. No sedative drug was utilized for epidural catheter placement. The BIS measurement was performed in both groups during the awake phase, before performing epidural anesthesia, and 10 minutes after epidural injection at 1-min intervals for 15 min. After induction of general anesthesia in both groups, anesthesia maintenance was established using the infusion of propofol with the aim of keeping the BIS level between 40 and 50 throughout the anesthesia. At the end of the study period, maintenance dose requirements of propofol and fentanyl were measured.
Thirty-two patients were enrolled in the study. There was no difference in BIS levels of the two groups in the awake phase. There was a significant difference between the propofol and fentanyl requirements of the two groups.
Performing CGEA using bupivacaine was reported to reduce propofol and fentanyl doses required to maintain BIS levels between 40 and 50 considerably.
PMCID: PMC3821134  PMID: 24223351
Anesthesia; Epidural; Bupivacaine
17.  Vocal local versus pharmacological treatments for pain management in tubal ligation procedures in rural Kenya: a non-inferiority trial 
BMC Women's Health  2014;14:21.
Vocal local (VL) is a non-pharmacological pain management technique for gynecological procedures. In Africa, it is usually used in combination with pharmacological analgesics. However, analgesics are associated with side-effects, and can be costly and subject to frequent stock-outs, particularly in remote rural settings. We compared the effectiveness of VL + local anesthesia + analgesics (the standard approach), versus VL + local anesthesia without analgesics, on pain and satisfaction levels for women undergoing tubal ligations in rural Kenya.
We conducted a site-randomised non-inferiority trial of 884 women receiving TLs from 40 Marie Stopes mobile outreach sites in Kisii and Machakos Districts. Twenty sites provided VL + local anesthesia + analgesics (control), while 20 offered VL + local anesthesia without additional analgesics (intervention). Pain was measured using a validated 11-point Numeric Rating Scale; satisfaction was measured using 11-point scales.
A total of 461 women underwent tubal ligations with VL + local anesthesia, while 423 received tubal ligations with VL + local anesthesia + analgesics. The majority were aged ≥30 years (78%), and had >3 children (99%). In a multivariate analysis, pain during the procedure was not significantly different between the two groups. The pain score after the procedure was significantly lower in the intervention group versus the control group (by 0.40 points; p = 0.041). Satisfaction scores were equally high in both groups; 96% would recommend the procedure to a friend.
VL + local anesthesia is as effective as VL + local anesthesia + analgesics for pain management during tubal ligation in rural Kenya. Avoiding analgesics is associated with numerous benefits including cost savings and fewer issues related to the maintenance, procurement and monitoring of restricted opioid drugs, particularly in remote low-resource settings where these systems are weak.
Trial registration
Pan-African Clinical Trials Registry PACTR201304000495942.
PMCID: PMC3916698  PMID: 24490628
Vocal local; Kenya; Family planning; Pain management; Tubal ligation
18.  The Influence of Injection Rate on the Hypnotic Effect of Propofol during Anesthesia: A Randomized Trial 
PLoS Clinical Trials  2006;1(3):e17.
Previous studies suggested that slow injection of propofol may increase the hypnotic effect during induction of anesthesia. The aim of the present study was therefore to investigate whether injection rate of propofol has an influence on its maximum effect.
Randomized, single-blind trial.
This study has been carried out in the operating rooms of a university hospital. An anesthesiologist and a resident performed the study with the aid of changing nursing staff.
We investigated 99 unpremedicated patients aged 18 to 60 years with American Society of Anesthesiologists (ASA) physical status 1–3.
Anesthesia was induced by intravenous injection of propofol (2 mg/kg). Propofol was manually injected in group 1 over a period of 5 s; in group 2 (120-s injection interval), and in group 3 (240-s injection interval), propofol was administered by an injection pump. After loss of consciousness, mask ventilation was performed with 100% oxygen. Bispectral index (BIS) was used to measure the hypnotic effect of propofol. After the decrease of BIS to the minimum value (i.e., maximum hypnotic effect) and the following increase of BIS to 60, the study period was finished and anesthesia was performed according to clinical criteria.
Outcome Measures:
We analyzed whether injection speed has an influence on the maximum hypnotic effect of a given dose of propofol (2 mg/kg).
BISmin marks the maximum electroencephalogram (EEG) effect of the propofol bolus as measured by the BIS. The lowest mean BISmin was measured in group 1 (28.7 ± 10.3). In group 2, BISmin was 33.0 (±13.9), and in group 3, BISmin was 36.4 (±11.0). There were no significant differences between group 2 and groups 1 or 3, but there were significant differences between groups 1 and 3. In group 1, BISmin was reached after 102.91 s (±44.20), in group 2 after 172.33 s (±29.76), and in group 3 after 274.21 s (±45.40). These differences were statistically significant for all comparisons. In summary, the lowest value for BISmin was achieved in the group with the fastest rate of propofol injection (group1, 5 s). The highest BISmin was obtained in the group with the slowest rate of injection (group 3, 240 s). The hemodynamic parameters were not significantly different among groups.
The hypnotic peak effect of propofol is lower with extremely slow injection (240 s versus 5 s). For clinically usual injection rates (5 s and 120 s), there was no significant difference in propofol peak effect.
Editorial Commentary
Background: Propofol is an injectable compound that is commonly used to bring about anesthesia in adults and in children aged more than three years. The rate at which propofol is injected is thought to affect the total dose of the drug that's needed to achieve loss of consciousness and lowered blood pressure during anesthesia. Previous trials have looked at the effect of different injection rates on anesthesia (time taken to lose consciousness, and degree of consciousness). In this trial of 99 patients scheduled for elective surgery, the researchers studied the effect of three different propofol injection rates. Patients were randomized to receive propofol injected over 5 s, 120 s, or 240 s. In each group the total dose of propofol (per kilogram of a patient's bodyweight) was the same. The main measure used to assess anesthetic effect was the bispectral index. This is a method of translating information from an electroencephalogram (graph showing electrical activity in the brain) into a standard measurement that reflects the patient's level of consciousness. The researchers also recorded time to loss of consciousness, i.e., when patients stopped responding to commands, and took blood pressure measurements.
What this trial shows: The researchers found that anesthetic effect, as measured using the bispectral index, was greatest in the patients who had received the fastest injections as compared with those who had received slower injections. However, the difference was only significant when comparing the fastest injection (5 seconds) with the slowest (240 seconds). In addition, the time taken to achieve anesthesia (as measured using the bispectral index), and time to loss of consciousness (as indicated by no response to commands), were lowest in patients who had the fastest injections; these differences were also significant. The researchers did not find an effect of the different injection rates on maximum and minimum blood pressure during the trial.
Strengths and limitations: The trial recruited enough patients to properly assess whether patients receiving different injection rates would have different responses to anesthesia. A limitation, acknowledged by the authors, is that the bispectral index uses a commercial computer program to interpret electroencephalograms and to produce a number value for anesthetic effect. Some evidence suggests that the output of the computer program may not correlate precisely with level of consciousness, and as the algorithm is not public, any irregularities in the way it works cannot be discovered by researchers outside the company. It is also of note that the slowest injection rate used by the researchers, 240 seconds, is not normally used in clinical practice.
Contribution to the evidence: The results of this study support those from a few other small randomized trials that faster injections of propofol achieve a larger anesthetic effect, and more quickly. However, the effect of injection rate on blood pressure is less clear; this study does not show any differences in the effect of injection rate on blood pressure, but other randomized trials have found an association.
PMCID: PMC1523225  PMID: 16878179
19.  Psychiatric diseases: Need for an increased awareness among the anesthesiologists 
Psychological disorders and psychiatric diseases have been on the rise since the last three decades. An increasing number of such patients are encountered nowadays for elective or emergency surgery. A multi-array of challenges are faced while anesthetizing these patients or treating them in an intensive care unit. The problems include the deteriorated mental physiology, altered cognition and the possible drug interactions with psychotropic medications. The challenge starts from the preoperative assessment stage. Knowledge of the pharmacological profile of the various anti-psychotic drugs, their side-effects and drug interactions are of prime importance for an anesthesiologist to facilitate smooth delivery of anesthesia in such patients. It is important to formulate a clear plan to deal with any challenge in the perioperative or postoperative period. All the clinical aspects and various definitions of mental disorders in the present article have been used as per the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). We reviewed the advances in psychiatric diseases, their treatment and their implications on delivery of anesthesia.
PMCID: PMC3214546  PMID: 22096274
Anxiety disorders; bipolar disorder; delirium; dementia; mood disorders; schizophrenia; substance abuse
20.  Usefulness of Intravenous Anesthesia Using a Target-controlled Infusion System with Local Anesthesia in Submuscular Breast Augmentation Surgery 
Archives of Plastic Surgery  2012;39(5):540-545.
Patients have anxiety and fear of complications due to general anesthesia. Through new instruments and local anesthetic drugs, a variety of anesthetic methods have been introduced. These methods keep hospital costs down and save time for patients. In particular, the target-controlled infusion (TCI) system maintains a relatively accurate level of plasma concentration, so the depth of anesthesia can be adjusted more easily. We conducted this study to examine whether intravenous anesthesia using the TCI system with propofol and remifentanil would be an effective method of anesthesia in breast augmentation.
This study recruited 100 patients who underwent breast augmentation surgery from February to August 2011. Intravenous anesthesia was performed with 10 mg/mL propofol and 50 µg/mL remifentanil simultaneously administered using two separate modules of a continuous computer-assisted TCI system. The average target concentration was set at 2 µg/mL and 2 ng/mL for propofol and remifentanil, respectively, and titrated against clinical effect and vital signs. Oxygen saturation, electrocardiography, and respiratory status were continuously measured during surgery. Blood pressure was measured at 5-minute intervals. Information collected includes total duration of surgery, dose of drugs administered during surgery, memory about surgery, and side effects.
Intraoperatively, there was transient hypotension in two cases and hypoxia in three cases. However, there were no serious complications due to anesthesia such as respiratory difficulty, deep vein thrombosis, or malignant hypertension, for which an endotracheal intubation or reversal agent would have been needed. All the patients were discharged on the day of surgery and able to ambulate normally.
Our results indicate that anesthetic methods, where the TCI of propofol and remifentanil is used, might replace general anesthesia with endotracheal intubation in breast augmentation surgery.
PMCID: PMC3474413  PMID: 23094252
Anesthesia, intravenous; Mammaplasty; Propofol; Remifentanil
21.  Comparison of meperidine and nefopam for prevention of shivering during spinal anesthesia 
Korean Journal of Anesthesiology  2013;64(3):229-233.
Shivering is a frequent event during spinal anesthesia and meperidine is a well-known effective drug for prevention and treatment of shivering. Nefopam is a non-opiate analgesic and also known to have an anti-shivering effect. We compared nefopam with meperidine for efficacy of prevention of shivering during spinal anesthesia.
Sixty five patients, American Society of Anesthesiologists physical status I or II, aged 20-65 years, scheduled for elective orthopedic surgery under spinal anesthesia were investigated. Patients were randomly divided into two groups, meperidine (Group M, n = 33) and nefopam (Group N, n = 32) groups. Group M and N received meperidine 0.4 mg/kg or nefopam 0.15 mg/kg, respectively, in 100 ml of isotonic saline intravenously. All drugs were infused for 15 minutes by a blinded investigator before spinal anesthesia. Blood pressures, heart rates, body temperatures and side effects were checked before and at 15, 30, and 60 minutes after spinal anesthesia.
The incidences and scores of shivering were similar between the two groups. The mean arterial pressures in Group N were maintained higher than in Group M at 15, 30, and 60 minutes after spinal anesthesia. The injection pain was checked in Group N only and its incidence was 15.6%.
We conclude that nefopam can be a good substitute for meperidine for prevention of shivering during spinal anesthesia with more stable hemodynamics, if injection pain is effectively controlled.
PMCID: PMC3611072  PMID: 23560188
Meperidine; Nefopam; Shivering; Spinal anesthesia
22.  Electroencephalographic Variation during End Maintenance and Emergence from Surgical Anesthesia 
PLoS ONE  2014;9(9):e106291.
The re-establishment of conscious awareness after discontinuing general anesthesia has often been assumed to be the inverse of loss of consciousness. This is despite the obvious asymmetry in the initiation and termination of natural sleep. In order to characterize the restoration of consciousness after surgery, we recorded frontal electroencephalograph (EEG) from 100 patients in the operating room during maintenance and emergence from general anesthesia. We have defined, for the first time, 4 steady-state patterns of anesthetic maintenance based on the relative EEG power in the slow-wave (<14 Hz) frequency bands that dominate sleep and anesthesia. Unlike single-drug experiments performed in healthy volunteers, we found that surgical patients exhibited greater electroencephalographic heterogeneity while re-establishing conscious awareness after drug discontinuation. Moreover, these emergence patterns could be broadly grouped according to the duration and rapidity of transitions amongst these slow-wave dominated brain states that precede awakening. Most patients progressed gradually from a pattern characterized by strong peaks of delta (0.5–4 Hz) and alpha/spindle (8–14 Hz) power (‘Slow-Wave Anesthesia’) to a state marked by low delta-spindle power (‘Non Slow-Wave Anesthesia’) before awakening. However, 31% of patients transitioned abruptly from Slow-Wave Anesthesia to waking; they were also more likely to express pain in the post-operative period. Our results, based on sleep-staging classification, provide the first systematized nomenclature for tracking brain states under general anesthesia from maintenance to emergence, and suggest that these transitions may correlate with post-operative outcomes such as pain.
PMCID: PMC4180055  PMID: 25264892
23.  Quality control and assurance in anesthesia: A necessity of the modern times 
The advent of newer developments in anesthesia techniques and current clinical scenario has necessitated assurance of quality anesthesia services delivery. Numerous factors including availability of newer drugs, availability of newer advanced monitoring gadgets, increased awareness among the patient population, implementation of newer medico-legal laws and professional competitiveness has mandated a quality control and assurance in anesthesia. These domains of quality control are adapted from public health and are being incorporated into daily anesthesia practice in a gradual and phased manner. Quality control and assurance can be assessed and measured with certain quality indicators, which are also helpful in determining the perioperative outcome in anesthesia and surgical practice. Patient's perception about various anesthetic procedures, drug effects and recovery state are the prime underlying basis for assessing the quality assurance and control. At the same time, a positive impact of feedback mechanism cannot be under-emphasized while aiming for improvement in delivery of quality anesthesia services. The current review is aimed at highlighting the important aspects associated with quality assurance and quality control in anesthesia practice.
PMCID: PMC4173622
Anesthesia; quality assurance; quality control; quality indicators
24.  Early Exposure to Anesthesia and Learning Disabilities in a Population-Based Birth Cohort 
Anesthesiology  2009;110(4):796-804.
Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. We studied association between anesthetic exposure prior to age 4 and the development of reading, written language and math learning disabilities (LD).
This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976–1982 and who remained in the community at 5 years of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, gender, and birth weight.
Of the 5,357 children in this cohort, 593 received general anesthesia before age 4. Compared to those not receiving anesthesia (N=4,764), a single exposure to anesthesia (N=449) was not associated with an increased risk of LD (hazard ratio =1.0, 95% CI 0.79–1.27). However, children receiving 2 anesthetics (N=100) or ≥3 anesthetics (N=44) were at increased risk for LD (hazard ratio =1.59, 95% CI 1.06–2.37, and hazard ratio =2.60, 95% CI 1.60–4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P=0.016).
Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. We cannot determine whether anesthesia itself may contribute to LD, or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.
PMCID: PMC2729550  PMID: 19293700
25.  Ultrasound-guided supraclavicular brachial plexus block in patient with halo device 
Saudi Journal of Anaesthesia  2010;4(1):20-22.
Ultrasound guided regional blocks are on the rise, many institutes are training their staff to master this technique of regional anesthesia. Regional anesthesia in case of an emergency surgery or elective surgery can be the best choice. The case described here is an example - patient with a halo fixation device after motor vehicle accident scheduled for surgery of the extremity. The main aim of management of this case is to achieve a safe anesthesia with minimal interference of the cervical fixation. Supraclavicular brachial plexus block is a good choice for surgeries of the arm and hand and use of an ultrasound to guide the block adds to the safety profile of this versatile block. It has been described as "Spinal of the upper limb". Patients with co-morbidities and injuries to the cervical spine are challenging cases to anesthetize, as regional anesthesia is a very attractive option, failure of the regional block will expose the patient to all adverse sequelae, which were being avoided by planning for a regional anesthesia. Ultrasound has revolutionized the way regional anesthesia is practiced and the proper drug can be placed at the right place in the hands of an experienced anesthesiologist and the block will help in avoiding all the complications of endotracheal anesthesia in these cases.
PMCID: PMC2900048  PMID: 20668562
Ultrasound; brachial plexus block; halo device

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