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1.  Dexmedetomidine and clonidine in epidural anaesthesia: A comparative evaluation 
Indian Journal of Anaesthesia  2011;55(2):116-121.
Efforts to find a better adjuvant in regional anaesthesia are underway since long. Aims and objectives are to compare the efficacy and clinical profile of two α-2 adrenergic agonists, dexmedetomidine and clonidine, in epidural anaesthesia with special emphasis on their sedative properties and an ability to provide smooth intra-operative and post-operative analgesia. A prospective randomized study was carried out which included 50 adult female patients between the ages of 44 and 65 years of (American Society of Anaesthesiologists) ASAI/II grade who underwent vaginal hysterectomies. The patients were randomly allocated into two groups; ropivacaine + dexmedetomidine (RD) and ropivacaine + clonidine (RC), comprising of 25 patients each. Group RD was administered 17 ml of 0.75% epidural ropivacaine and 1.5 μg/kg of dexmedetomidine, while group RC received admixture of 17 ml of 0.75% ropivacaine and 2 μg/kg of clonidine. Onset of analgesia, sensory and motor block levels, sedation, duration of analgesia and side effects were observed. The data obtained was subjected to statistical computation with analysis of variance and chi-square test using statistical package for social science (SPSS) version 10.0 for windows and value of P < 0.05 was considered significant and P < 0.0001 as highly significant. The demographic profile, initial and post-operative block characteristics and cardio-respiratory parameters were comparable and statistically non-significant in both the groups. However, sedation scores with dexmedetomidine were better than clonidine and turned out to be statistically significant (P < 0.05). The side effect profile was also comparable with a little higher incidence of nausea and dry mouth in both the groups which was again a non-significant entity (P > 0.05). Dexmedetomidine is a better neuraxial adjuvant compared to clonidine for providing early onset of sensory analgesia, adequate sedation and a prolonged post-operative analgesia.
PMCID: PMC3106381  PMID: 21712865
Clonidine; dexmedetomidine; epidural anaesthesia; ropivacaine; vaginal hysterectomy
2.  Arousal time from sedation during spinal anaesthesia for elective infraumbilical surgeries: Comparison between propofol and midazolam 
Indian Journal of Anaesthesia  2014;58(4):403-409.
Background and Aims:
Studies have already compared propofol and midazolam as sedatives during regional anaesthesia. A few studies have focused on recovery characteristics and very few have utilised both instrumental and clinical sedation monitoring for assessing recovery time. This study was designed primarily to compare arousal time from sedation using propofol with that of midazolam during spinal anaesthesia for infraumbilical surgeries, while depth of sedation was monitored continuously with bispectral index (BIS) monitor. The correlation between the BIS score and observer's assessment of awareness/sedation (OAA/S) score during recovery from sedation was also studied.
A total of 110 patients were randomly assigned to receive either propofol (Group P, n = 55) or midazolam (Group M, n = 55). Patients in the Group P received bolus of propofol (1 mg/kg), followed by infusion at 3 mg/kg/h; Group M received bolus of midazolam (0.05 mg/kg), followed by infusion at 0.06 mg/kg/h and titration until BIS score 70 was achieved and maintained between 65 and 70. OAA/S score was noted at BIS 70 and again at BIS 90 during recovery. The time to achieve OAA/S score 5 was noted. Spearman's correlation was calculated between the arousal time from sedation and the time taken to reach an OAA/S score of 5 in both the study groups.
Arousal time from sedation was found lower for Group P compared to Group M (7.54 ± 3.70 vs. 15.54 ± 6.93 min, respectively, P = 0.000). The time taken to reach OAA/S score 5 was also found to be lower for Group P than Group M (6.81 ± 2.54 min vs. 13.51 ± 6.24 min, respectively, P = 0.000).
A shorter arousal time from sedation during spinal anaesthesia can be achieved using propofol compared with midazolam, while depth of sedation was monitored with BIS monitor and OAA/S score. Both objective and clinical scoring correlate strongly during recovery from sedation.
PMCID: PMC4155284  PMID: 25197107
Bispectral index monitoring; midazolam; propofol; sedation; spinal anaesthesia
3.  Effect of ketamine pretreatment for anaesthesia in patients undergoing percutaneous transluminal balloon angioplasty with continuous remifentanil infusion 
Korean Journal of Anesthesiology  2011;61(4):308-314.
An appropriate level of sedation and pharmacological assist are essential during percutaneous transluminal balloon angioplasty (PTA). Ketamine provides good analgesia while preserving airway patency, ventilation, and cardiovascular stability with an opioid sparing effect suggesting that it would be ideal in combination with remifentanil and midazolam in spontaneously breathing patients. We evaluated the effect of a small dose of ketamine added to midazolam and remifentanil on analgesia/sedation for PTA procedures.
Sixty-four patients receiving PTA were enrolled. The Control group received midazolam 1.0 mg i.v. and continuous infusion of remifentanil 0.05 µg/kg/min. The Ketamine group received, in addition, an intravenous bolus of 0.5 mg/kg ketamine. Patients' haemodynamic data were monitored before remifentanil infusion, 5 min after remifentanil infusion, at 1, 3, 5, 30 min after incision, and at admission to the recovery room. Verbal numerical rating scales (VNRS) and sedation [OAA/S (Observer's Assessment of Alertness/Sedation)] scores were also recorded.
The VNRS values at 1, 3, and 5 min after incision and OAA/S scores at 5 min after remifentanil infusion, and 1, 3, and 5 min after incision were lower in the Ketamine group than in the Control group. In the Control group, the VNRS value at 1 min after incision significantly increased and OAA/S values at 3, 5, and 30 min after incision significantly decreased compared to baseline values, while there were no significant changes in the ketamine group.
A small dose of ketamine as an adjunct sedative to the combination of midazolam and remifentanil produced a better quality of sedation and analgesia than without ketamine and provided stable respiration without cardiopulmonary deterioration.
PMCID: PMC3219777  PMID: 22110884
Ketamine; Pain scale; Remifentanil; Sedation
4.  Brainstem auditory evoked potentials in cattle sedated with xylazine 
This study examined the effect of sedation with xylazine on the brainstem auditory evoked potentials (BAEP) of cattle to determine whether sedation causes differences in waveform configuration, peak latencies, interpeak latencies, measurement time of the average count (2000 responses), and clinical signs. There were no significant differences between the sedation and no-sedation groups in peak latency of any stimulus intensities. In the sedation group, the baselines of waveforms were comparatively stabilized. Those in the no-sedation group were unstable, however, because the measurement can be influenced by excessive muscle movement. The present findings suggest that clinically, it is useful to use a sedative when measuring BAEP in cattle to control excessive movement of the cattle without influencing the peak latencies.
PMCID: PMC2327241  PMID: 18505193
5.  Bispectral index score and observer's assessment of awareness/sedation score may manifest divergence during onset of sedation: Study with midazolam and propofol 
Indian Journal of Anaesthesia  2013;57(4):351-357.
Correlation between the clinical and electroencephalogram-based monitoring has been documented sporadically during the onset of sedation. Propofol and midazolam have been studied individually using the observer's assessment of awareness/sedation (OAA/S) score and Bispectral index score (BIS). The present study was designed to compare the time to onset of sedation for propofol and midazolam using both BIS and OAA/S scores, and to find out any correlation.
A total of 46 patients (18-60 years, either sex, American Society of Anesthesiologists (ASA) I/II) posted for infraumbilical surgeries under spinal anaesthesia were randomly allocated to receive either injection propofol 1 mg/kg bolus followed by infusion 3 mg/kg/h (Group P, n=23) or injection midazolam 0.05 mg/kg bolus followed by infusion 0.06 mg/kg/h (Group M, n=23). Spinal anaesthesia was given with 2.5 ml to 3.0 ml of 0.5% bupivacaine heavy. When sensory block reached T6 level, sedation was initiated. The time to reach BIS score 70 and time to achieve OAA/S score 3 from the start of study drug were noted. OAA/S score at BIS score 70 was noted. Data from 43 patients were analyzed using SPSS 12 for Windows.
Time to reach BIS score 70 using propofol was significantly lower than using the midazolam (P<0.05). Time to achieve OAA/S score 3 using propofol was comparable with midazolam (P=0.358).
A divergence exists between the time to reach BIS score 70 and time to achieve OAA/S score 3 using midazolam, compared with propofol, during the onset of sedation.
PMCID: PMC3800326  PMID: 24163448
Bispectral index score; midazolam; observer's assessment of awareness/sedation score; propofol; sedation
6.  Evaluation of brain stem auditory evoked potentials in stable patients with chronic obstructive pulmonary disease 
Annals of Thoracic Medicine  2008;3(4):128-134.
Though there are few studies addressing brainstem auditory evoked potentials (BAEP) in patients with chronic obstructive pulmonary disease (COPD), subclinical BAEP abnormalities in stable COPD patients have not been studied. The present study aimed to evaluate the BAEP abnormalities in this study group.
In the present study, 80 male subjects were included: COPD group comprised 40 smokers with stable COPD with no clinical neuropathy; 40 age-matched healthy volunteers served as the control group. Latencies of BAEP waves I, II, III, IV, and V, together with interpeak latencies (IPLs) of I-III, I-V, and III-V, and amplitudes of waves I-Ia and V-Va were studied in both the groups to compare the BAEP abnormalities in COPD group; the latter were correlated with patient characteristics and Mini–Mental Status Examination Questionnaire (MMSEQ) scores to seek any significant correlation.
Twenty-six (65%) of the 40 COPD patients had BAEP abnormalities. We observed significantly prolonged latencies of waves I, III, V over left ear and waves III, IV, V over right ear; increased IPLs of I-V, III-V over left ear and of I-III, I-V, III-V over right side. Amplitudes of waves I-Ia and V-Va were decreased bilaterally. Over left ear, the latencies of wave I and III were significantly correlated with FEV1; and amplitude of wave I-Ia, with smoking pack years. A weak positive correlation between amplitude of wave I-Ia and duration of illness; and a weak negative correlation between amplitude of wave V-Va and MMSEQ scores were seen over right side.
We observed significant subclinical BAEP abnormalities on electrophysiological evaluation in studied stable COPD male patients having mild-to-moderate airflow obstruction.
PMCID: PMC2700451  PMID: 19561894
Brainstem auditory evoked potentials; chronic obstructive pulmonary disease; correlation analysis; Mini–Mental Status Examination
7.  Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine 
Indian Journal of Anaesthesia  2013;57(3):265-269.
Intravenous (IV) dexmedetomidine with excellent sedative properties has been shown to reduce analgesic requirements during general anaesthesia. A study was conducted to assess the effects of IV dexmedetomidine on sensory, motor, haemodynamic parameters and sedation during subarachnoid block (SAB).
A total of 50 patients undergoing infraumbilical and lower limb surgeries under SAB were selected. Group D received IV dexmedetomidine 0.5 mcg/kg bolus over 10 min prior to SAB, followed by an infusion of 0.5 mcg/kg/h for the duration of the surgery. Group C received similar volume of normal saline infusion. Time for the onset of sensory and motor blockade, cephalad level of analgesia and duration of analgesia were noted. Sedation scores using Ramsay Sedation Score (RSS) and haemodynamic parameters were assessed.
Demographic parameters, duration and type of surgery were comparable. Onset of sensory block was 66±44.14 s in Group D compared with 129.6±102.4 s in Group C. The time for two segment regression was 111.52±30.9 min in Group D and 53.6±18.22 min in Group C and duration of analgesia was 222.8±123.4 min in Group D and 138.36±21.62 min in Group C. The duration of motor blockade was prolonged in Group D compared with Group C. There was clinically and statistically significant decrease in heart rate and blood pressures in Group D. The mean intraoperative RSS was higher in Group D.
Administration of IV dexmedetomidine during SAB hastens the onset of sensory block and prolongs the duration of sensory and motor block with satisfactory arousable sedation.
PMCID: PMC3748681  PMID: 23983285
Dexmedetomidine; intravenous; subarachnoid block; supplementation
8.  Spectral entropy as an objective measure of sedation state in midazolam-premedicated patients 
Saudi Journal of Anaesthesia  2012;6(2):131-135.
Objective assessment of sedation depth is a valuable target. Spectral entropy is an anesthetic depth monitor based on the analysis of the electroencephalogram signal.
To evaluate the performance of spectral entropy as an objective measure of sedation state in midazolam-premedicated patients and to correlate it with a clinically assessed sedation score.
Settings and Design:
This prospective double-blind placebo-controlled study was performed in King Fahd Hospital of the university.
Eighty adult ASA I–II patients were randomly assigned into 4 groups. Patients were premedicated using 0.02, 0.04, or 0.06 mg/kg midazolam or saline intramuscularly. The effect of these doses on the Observer's Assessment of Alertness and Sedation (OAA/S) scale, hemodynamic variables, response entropy (RE), and state entropy (SE), was evaluated at 10, 20, and 30 min after premedication.
Statistical analysis:
Spearman Rank-order correlation analysis to examine the relation between OAA/S and entropy. The ability of spectral entropy to predict the depth of sedation was evaluated using Smith prediction probability.
Midazolam doses ≥0.04 mg/kg produced significant decreases in RE, SE, and OAA/S scores. There was a strong correlation between midazolam dose and OAA/S scale, RE, and SE since Spearman Rank R values were 0.792, 0.822, and 0.745, respectively (P<0.001). In addition, RE and SE were strong predictors of OAA/S level during midazolam sedation with no significant difference in prediction between the 2 entropy components.
Spectral entropy is a reliable measure for the sedative premedication. It may be used to objectively assess the adequacy of midazolam premedication and to determine the dose requirement.
PMCID: PMC3385254  PMID: 22754438
Monitoring; depth of anaesthesia; observer's assessment of alertness and sedation; premedication; midazolam; sedation
9.  The combined monitoring of brain stem auditory evoked potentials and intracranial pressure in coma. A study of 57 patients. 
Continuous monitoring of brainstem auditory evoked potentials (BAEPs) was carried out in 57 comatose patients for periods ranging from 5 hours to 13 days. In 53 cases intracranial pressure (ICP) was also simultaneously monitored. The study of relative changes of evoked potentials over time proved more relevant to prognosis than the mere consideration of "statistical normality" of waveforms; thus progressive degradation of the BAEPs was associated with a bad outcome even if the responses remained within normal limits. Contrary to previous reports, a normal BAEP obtained during the second week of coma did not necessarily indicate a good vital outcome; it could, however, do so in cases with a low probability of secondary insults. The simultaneous study of BAEPs and ICP showed that apparently significant (greater than 40 mm Hg) acute rises in ICP were not always followed by BAEP changes. The stability of BAEP's despite "significant" ICP rises was associated in our patients with a high probability of survival, while prolongation of central latency of BAEPs in response to ICP modifications was almost invariably followed by brain death. Continuous monitoring of brainstem responses provided a useful physiological counterpart to physical parameters such as ICP. Serial recording of cortical EPs should be added to BAEP monitoring to permit the early detection of rostrocaudal deterioration.
PMCID: PMC1015104  PMID: 1402970
10.  Correlation between Bispectral Index, Observational Sedation Scale, and Lower Esophageal Sphincter Pressure in volunteers using dexmedetomidine or propofol 
Many anesthetics reduce lower esophageal sphincter pressure (LESP) and consequently the gastro-esophageal pressure gradient (GEPG); thus they may promote gastro-esophageal reflux and contribute to aspiration pneumonia. Our goals were to evaluate the association between LESP and 2 measures of sedation: bispectral index (BIS) and the responsiveness component of the Observer’s Assessment of Alertness score (OAA/S).
Eleven healthy volunteers were each sedated on 2 separate days. Subjects were given sedative infusions of increasing target plasma concentrations of dexmedetomidine or propofol. LESP and GEPG were recorded after starting each infusion phase. Generalized estimating equation modeling was used to assess the relationship between LESP and, respectively, BIS and OAA/S. The existence of a drug-dependent association was evaluated within these models by testing an interaction term. Wald tests were used to evaluate the relationships within the models.
We found a significant relationship between LESP and BIS (P=0.0043) after adjusting for the main effect of sedative type – a deepening of sedation as measured by a decrease in BIS of 10% was associated with a decrease [Bonferroni-adjusted 95% CI] in LESP of −1.34 [−2.39, −0.29] mmHg. After adjusting for the main effect of sedative drug, LESP significantly declined with declining OAA/S (P=0.001); a unit decrease of OAA/S was associated with a decrease [Bonferroni-adjusted 95% CI] in LESP of −2.01 [−3.20, −0.81] mmHg.
Deeper sedation, as measured by either BIS or OAA/S, significantly reduces LESP.
PMCID: PMC3560568  PMID: 23018351
BIS; lower esophageal sphincter; dexmedetomidine; propofol
11.  A Comparative Study of Two Different Doses of Epidural Neostigmine Coadministered with Lignocaine for Post Operative Analgesia and Sedation 
Adjuvants have been used to prolong analgesic effects of epidural local anaesthetics. We studied two different doses of neostigmine.
Patients & Methods:
A randomized double blind study was conducted on ninety adult females scheduled for lower intra abdominal surgeries. The study was designed to compare two doses of epidural neostigmine co administered with lignocaine, with regard to its analgesic efficacy and its effect on sedation in postoperative period. Patients were divided into three groups of 30 each. Group I received lignocaine 1% (9ml) with normal saline (1ml), group II lignocaine1% (9ml) with neostigmine 100μg in saline (1ml) and group III received lignocaine 1% (9ml) with neostigmine 200μg in NS (1ml). Group I served as a control. In operating room, after putting epidural catheter, general anesthesia was administered with propofol (2mg kg-1), succinylcholine (2mg kg-1) and maintained with O2, N2O, relaxant technique. At the end of surgery, patients were reversed. Epidural analgesic medication was administered to after proper recovery from anesthesia. Intensity of pain relief on VAS, duration of analgesia, level of sensory block, motor blockade, sedation by sedation score and complications were assessed.
The addition of neostigmine resulted in significant longer duration of analgesia (dose independent) and sedation (dose dependent). Sensory and motor blockade were identical in all three groups. There was no incidence of respiratory depression, pruritus, bradycardia or hypotension in any group. Two patients in control group and one, receiving neostigmine (200μg), developed nausea/vomiting.
Co administration of epidural neostigmine and lignocaine appears to be a useful technique for postoperative analgesia as it increases the duration of analgesia and provides desirable sedation at the same time.
PMCID: PMC3087256  PMID: 21547170
Anesthesia; Epidural analgesia; Lignocaine; Neostigmine; Sedation
12.  Verapamil-induced changes in central conduction in patients with multiple sclerosis. 
The electrophysiological characteristics of demyelinated axons are sensitive to changes in plasma calcium concentration. This study investigated the effect of verapamil, a calcium antagonist drug, on brainstem auditory, visual, and somatosensory evoked potentials in multiple sclerosis patients. Eight clinically stable patients with abnormal visual and/or brainstem auditory evoked potentials and four normal volunteers were studied. During intravenous infusions of verapamil (mean plasma concentration = 130.0 +/- 56.4 ng/ml), the latencies of peaks III and V were shortened (p less than 0.05) in multiple sclerosis patients with abnormally prolonged BAEPs. The I-III (delta = 0.08 ms), III-V (delta = 0.46 ms), and I-V (delta = 0.53 ms) interpeak intervals, and the P100 latency (delta = 10.15 ms) of the visual evoked potential were similarly affected in these patients. In contrast, normal evoked potentials of both multiple sclerosis patients and control subjects were not altered compared to baseline recordings obtained 24 hours earlier. Intravenous verapamil, therefore, alters the BAEPs and VEPs of some multiple sclerosis patients with demyelinated auditory and visual pathways by shortening pathologically prolonged latencies toward normal. The present study suggests pharmacological manipulation of calcium-dependent processes, possibly at the level of the demyelinated axon, can acutely facilitate central conduction of electrical impulses in some patients with clinically stable multiple sclerosis.
PMCID: PMC1028574  PMID: 3001232
13.  Changes in brainstem auditory evoked potentials among North Indian females with Type 2 diabetes mellitus 
Diabetes mellitus is a complex metabolic disorder whose detrimental effects on various organ systems, including the nervous system are well known.
This study was conducted to determine the changes in the brainstem auditory evoked potentials (BAEP) in patients with type 2 diabetes mellitus.
Materials and Methods:
In this case-control study, 116 females with type 2 diabetes and 100 age matched, healthy female volunteers were selected. The brainstem auditory evoked potentials (BAEP) were recorded with RMS EMG EP Marc-II Channel machine. The measures included latencies of waves I, II, III, IV, V and Interpeak latencies (IPL) I-III, III-V and I-V separately for both ears. Data was analysed statistically with SPSS software v13.0.
It was found that IPL I-III was significantly delayed (P = 0.028) only in the right ear, while the latency of wave V and IPL I-V showed a significant delay bilaterally (P values for right ear being 0.021 and 0.0381 respectively while those for left ear being 0.028 and 0.016 respectively), in diabetic females. However, no significant difference (P > 0.05) was found between diabetic and control subjects as regards to the latencies of waves I, II, III, IV and IPL III-V bilaterally and IPL I-III unilaterally in the left ear. Also, none of the BAEP latencies were significantly correlated with either the duration of disease or with fasting blood glucose levels in diabetics.
Therefore, it could be concluded that diabetes patients have an early involvement of central auditory pathway, which can be detected quite accurately with the help of auditory evoked potential studies.
PMCID: PMC3872679  PMID: 24381878
Auditory evoked potentials; brainstem dysfunction; diabetes mellitus; interpeak latency; sensorineural hearing loss
14.  Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries 
Saudi Journal of Anaesthesia  2011;5(4):365-370.
Background and Aims:
Opioids as epidural adjunct to local anesthetics (LA) have been in use since long and α-2 agonists are being increasingly used for similar purpose. The present study aims at comparing the hemodynamic, sedative, and analgesia potentiating effects of epidurally administered fentanyl and dexmedetomidine when combined with ropivacaine.
A total of one hundred patients of both gender aged 21-56 years, American Society of Anaesthesiologist (ASA) physical status I and II who underwent lower limb orthopedic surgery were enrolled into the present study. Patients were randomly divided into two groups: Ropivacaine + Dexmedetomidine (RD) and Ropivacaine + Fentanyl (RF), comprising 50 patie nts each. Inj. Ropivacaine, 15 ml of 0.75%, was administered epidurally in both the groups with addition of 1 μg/kg of dexmedetomidine in RD group and 1 μg/kg of fentanyl in RF group. Besides cardio-respiratory parameters and sedation scores, various block characteristics were also observed which included time to onset of analgesia at T10, maximum sensory analgesic level, time to complete motor blockade, time to two segmental dermatomal regressions, and time to first rescue analgesic. At the end of study, data was compiled systematically and analyzed using ANOVA with post-hoc significance, Chi-square test and Fisher's exact test. Value of P<0.05 is considered significant and P<0.001 as highly significant.
The demographic profile of patients was comparable in both the groups. Onset of sensory analgesia at T10 (7.12±2.44 vs 9.14±2.94) and establishment of complete motor blockade (18.16±4.52 vs 22.98±4.78) was significantly earlier in the RD group. Postoperative analgesia was prolonged significantly in the RD group (366.62±24.42) and consequently low dose consumption of local anaesthetic LA (76.82±14.28 vs 104.35±18.96) during epidural top-ups postoperatively. Sedation scores were much better in the RD group and highly significant on statistical comparison (P<0.001). Incidence of nausea and vomiting was significantly high in the RF group (26% and 12%), while incidence of dry mouth was significantly higher in the RD group (14%) (P<0.05).
Dexmedetomidine seems to be a better alternative to fentanyl as an epidural adjuvant as it provides comparable stable hemodynamics, early onset, and establishment of sensory anesthesia, prolonged post-op analgesia, lower consumption of post-op LA for epidural analgesia, and much better sedation levels.
PMCID: PMC3227304  PMID: 22144922
Dexmedetomidine; epidural anesthesia; fentanyl; lower limb surgery; ropivacaine
15.  Comparative evaluation of ropivacaine versus dexmedetomidine and ropivacaine in epidural anesthesia in lower limb orthopedic surgeries 
Saudi Journal of Anaesthesia  2014;8(4):463-469.
Various adjuvant are being used with local anesthetics for prolongation of intra operative and postoperative analgesia in epidural block for lower limb surgeries. Dexmedetomidine, the highly selective α2 adrenergic agonist is a new neuroaxial adjuvant gaining popularity. The aim of the present study was to compare the hemodynamic, sedative and analgesia potentiating effects of epidurally administered dexmedetomidine when combined with ropivacaine.
Materials and Methods:
The study was conducted in prospective, randomized double-blind manner in which 100 patients of American Society of Anesthesiologist Grade I and II in the age group of 20-65 years of either sex under going lower limb surgeries were included after taking informed consent. The patients were randomly allocated into two groups of 50 each. Epidural anesthesia was given with 150 mg of 0.75% ropivacaine in Group A (n = 50) and 150 mg of 0.75% ropivacaine with dexmedetomidine (1 μg/kg) in Group B (n = 50). Two groups were compared with respect to hemodynamic changes, block characteristics which included time to onset of analgesia at T10, maximum sensory analgesic level, time to maximum sensory and motor block, time to regression at S1 dermatome and time to the first dose of rescue analgesia for 24 h. At the end of study, data was compiled and analyzed statistically using Chi-square test, Fisher's exact test and Student t-test. P < 0.05 was considered to be significant and P < 0.001 as highly significant.
Significant difference was observed in relation to the duration of sensory block (375.20 ± 15.97 min in Group A and 535.18 ± 19.85 min in Group B [P - 0.000]), duration of motor block (259.80 ± 15.48 min in Group A and 385.92 ± 17.71 min in Group B [P - 0.000]), duration of post-operative analgesia (312.64 ± 16.21 min in Group A and 496.56 ± 16.08 min in Group B [P < 0.001]) and consequently low doses of rescue analgesia in Group B (1.44 ± 0.501) as compared to Group A (2.56 ± 0.67). Sedation score was significantly more in Group B in the post-operative period.
Epidural Dexmedetomidine as an adjuvant to Ropivacaine is associated with prolonged sensory and motor block, hemodynamic stability, prolonged postoperative analgesia and reduced demand for rescue analgesics when compared to plain Ropivacaine.
PMCID: PMC4236931  PMID: 25422602
Dexmedetomidine; epidural anesthesia; lower limb orthopedic surgery; ropivacaine
16.  Spectral entropy for assessing the depth of propofol sedation 
Korean Journal of Anesthesiology  2012;62(3):234-239.
For patients in the intensive care unit (ICU) or under monitored anesthetic care (MAC), the precise monitoring of sedation depth facilitates the optimization of dosage and prevents adverse complications from underor over-sedation. For this purpose, conventional subjective sedation scales, such as the Observer's Assessment of Alertness/Sedation (OAA/S) or the Ramsay scale, have been widely utilized. Current procedures frequently disturb the patient's comfort and compromise the already well-established sedation. Therefore, reliable objective sedation scales that do not cause disturbances would be beneficial. We aimed to determine whether spectral entropy can be used as a sedation monitor as well as determine its ability to discriminate all levels of propofol-induced sedation during gradual increments of propofol dosage.
In 25 healthy volunteers undergoing general anesthesia, the values of response entropy (RE) and state entropy (SE) corresponding to each OAA/S (5 to 1) were determined. The scores were then analyzed during each 0.5 mcg/ml- incremental increase of a propofol dose.
We observed a reduction of both RE and SE values that correlated with the OAA/S (correlation coefficient of 0.819 in RE-OAA/S and 0.753 in SE-OAA/S). The RE and SE values corresponding to awake (OAA/S score 5), light sedation (OAA/S 3-4) and deep sedation (OAA/S 1-2) displayed differences (P < 0.05).
The results indicate that spectral entropy can be utilized as a reliable objective monitor to determine the depth of propofol-induced sedation.
PMCID: PMC3315652  PMID: 22474549
Entropy; Propofol; Sedation
17.  The analgesic effect of midazolam when added to lidocaine for intravenous regional anaesthesia* 
Midazolam has analgesic properties. The aim of the present study was to assess the analgesic effect of midazolam when added to lidocaine in intravenous regional anesthesia (IVRA).
Sixty patients undergoing hand surgery were randomly allocated into two groups to receive 3 mg/kg 2% lidocaine diluted with saline to a total volume of 40 mL in the control group (group lidocaine saline ~ LS, n=30) or 50 μg/kg midazolam plus 3 mg/kg 2% lidocaine diluted with saline to a total volume of 40 mL in the midazolam group (group lidocaine midazolam ~ LM, n=30). Before and after the tourniquet application, hemodynamic variables, tourniquet pain, sedation, and analgesic use were recorded.
Shortened sensory and motor block onset time [4.20 (0.84) vs. 5.94 (0.83) min, p = 0.001 and 6.99 (0.72) vs. 9.07 (0.99) min, p = 0.001 in LM and LS groups, respectively], prolonged sensory and motor block recovery times [8.41 (0.94) vs. 5.68 (0.90) min, p = 0.001 and 11.85 (1.18) vs. 7.06 (0.82) min, p = 0.001 in LM and LS groups, respectively], shortened visual analog scale (VAS) scores of tourniquet pain (p < 0.05), and improved quality of anesthesia were found in group LM (p < 0.05). VAS scores were lower in group LM in the postoperative period (p = 0.001). Postoperative analgesic requirements were significantly smaller in group LM (p = 0.001).
The addition of 50 μg/kg midazolam to lidocaine for IVRA shortens the onset of sensory and motor block, and improves quality of anesthesia and perioperative analgesia without causing side effects.
PMCID: PMC3430038  PMID: 22973382
Anaesthetic Techniques; IV Regional Lidocaine; Postoperative; Analgesics; Midazolam; Tourniquet Pain
18.  Nitrous Oxide Sedation and Bispectral Index 
European journal of dentistry  2007;1(4):240-245.
To determine whether bispectral analysis (BIS) changes during nitrous oxide (N2O) sedation in anxious children undergoing extraction of primary teeth.
In this prospective study 45, ASA physical status I children, aged between 7 to 12 years and scheduled for primary teeth extraction under N2O/O2 sedation are included. At baseline (T0) and during the sedation procedure (T1-6); BIS levels, Ramsay Sedation Scores (RSS), oxygen saturation (Sp02), and heart rate (HR) were recorded at one-minute intervals. Forty percent N2O in O2 was given by a nasal hood, and N2O concentration was enhanced to 60% in a two-minute period. Paired measurements of BIS levels with Observer’s Assessment of Alertness and Sedation (OAA/S) scores were obtained during sedation procedure.
Since 5 patients refused application of the nasal hood, a total 40 of the original 45 subjects completed the study. Mean age and weight of the children were 9.5 ± 1.4 years and 23.7 ± 9.7 kg, respectively. Nitrous oxide inhalation produced no changes in BIS levels despite a sedation level in OAA/S scores were observed at 40–60% N2O concentrations.
BIS values do not change during N2O/O2 sedation and the BIS monitor is not appropriate to evaluate the depth of sedation provided by N2O/O2 during primary teeth extraction in children.
PMCID: PMC2609910  PMID: 19212474
Nitrous oxide sedation; Bispectral index; Anxiety; Ramsay sedation scale
19.  Assessment of visual and auditory evoked potentials in multiple sclerosis patients with and without fatigue 
Neurological Sciences  2014;36:235-242.
The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I–V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients.
PMCID: PMC4303713  PMID: 25240278
Multiple sclerosis; Fatigue; Evoked potentials
20.  Deep sedation during gastrointestinal endoscopy: Propofol-fentanyl and midazolam-fentanyl regimens 
AIM: To compare deep sedation with propofol-fentanyl and midazolam-fentanyl regimens during upper gastrointestinal endoscopy.
METHODS: After obtaining approval of the research ethics committee and informed consent, 200 patients were evaluated and referred for upper gastrointestinal endoscopy. Patients were randomized to receive propofol-fentanyl or midazolam-fentanyl (n = 100/group). We assessed the level of sedation using the observer’s assessment of alertness/sedation (OAA/S) score and bispectral index (BIS). We evaluated patient and physician satisfaction, as well as the recovery time and complication rates. The statistical analysis was performed using SPSS statistical software and included the Mann-Whitney test, χ2 test, measurement of analysis of variance, and the κ statistic.
RESULTS: The times to induction of sedation, recovery, and discharge were shorter in the propofol-fentanyl group than the midazolam-fentanyl group. According to the OAA/S score, deep sedation events occurred in 25% of the propofol-fentanyl group and 11% of the midazolam-fentanyl group (P = 0.014). Additionally, deep sedation events occurred in 19% of the propofol-fentanyl group and 7% of the midazolam-fentanyl group according to the BIS scale (P = 0.039). There was good concordance between the OAA/S score and BIS for both groups (κ = 0.71 and κ = 0.63, respectively). Oxygen supplementation was required in 42% of the propofol-fentanyl group and 26% of the midazolam-fentanyl group (P = 0.025). The mean time to recovery was 28.82 and 44.13 min in the propofol-fentanyl and midazolam-fentanyl groups, respectively (P < 0.001). There were no severe complications in either group. Although patients were equally satisfied with both drug combinations, physicians were more satisfied with the propofol-fentanyl combination.
CONCLUSION: Deep sedation occurred with propofol-fentanyl and midazolam-fentanyl, but was more frequent in the former. Recovery was faster in the propofol-fentanyl group.
PMCID: PMC3683682  PMID: 23801836
Endoscopy; Deep sedation; Anesthetic administration; Anesthetic dose; Adverse effects
21.  Right thoracic paravertebral anaesthesia for percutaneous radiofrequency ablation of liver tumours 
The British Journal of Radiology  2011;84(1005):785-789.
Percutaneous radiofrequency ablation (PRFA) of liver tumours performed under local anaesthesia and intravenous sedation can cause severe pain to patients. This prospective study evaluated the efficacy of a right thoracic paravertebral block (TPVB) for anaesthesia and analgesia during PRFA of liver tumours.
20 patients, aged 44–74 years, with liver malignancies received a multiple injection TPVB at the T6–10 levels 30 min before the PRFA. An intravenous infusion of propofol (3–5 mg kg–1 h–1) was administered to patients who requested to be sedated and intravenous fentanyl (25 µg bolus) was administered as rescue analgesia. Pain during the TPVB and PRFA was assessed using a numerical rating scale (NRS; 0, no pain; 10, worst imaginable pain). Patients were also assessed for residual pain and analgesic consumption during the 24 h after the intervention.
The TPVB was well tolerated and produced ipsilateral sensory anaesthesia with satisfactory spread (median (range); 8 (6–11) dermatomes). The PRFA procedure caused mild pain (mean (standard deviation, SD); NRS 1.4 (1.9)) during the insertion of the ablation needle and the peak pain intensity during the therapeutic burn was moderate (mean (SD); NRS 5.0 (3.3)) in severity. During the 24 h after the PRFA, patients reported minimal pain and consumed very few analgesics. The mean (SD) satisfaction score (0, totally dissatisfied; 10, very satisfied) of the patients was 8.9 (1.1) and that of the radiologists was 8.8 (1.4).
A right TPVB is safe and effective for anaesthesia and analgesia during PRFA of malignant liver tumours.
PMCID: PMC3473782  PMID: 21081575
22.  Enhanced Auditory Brainstem Response and Parental Bonding Style in Children with Gastrointestinal Symptoms 
PLoS ONE  2012;7(3):e32913.
The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS) are unclear. We hypothesized that children with chronic gastrointestinal (GI) symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP) responses and receive more inadequate parental bonding.
Methodology/Principal Findings
Children aged seven and their mothers (141 pairs) participated. BAEP was measured by summation of 1,000 waves of the electroencephalogram triggered by 75 dB click sounds. The mothers completed their Children's Somatization Inventory (CSI) and Parental Bonding Instrument (PBI). CSI results revealed 66 (42%) children without GI symptoms (controls) and 75 (58%) children with one or more GI symptoms (GI group). The III wave in the GI group (median 4.10 interquartile range [3.95–4.24] ms right, 4.04 [3.90–4.18] ms left) had a significantly shorter peak latency than controls (4.18 [4.06–4.34] ms right, p = 0.032, 4.13 [4.02–4.24] ms left, p = 0.018). The female GI group showed a significantly shorter peak latency of the III wave (4.00 [3.90–4.18] ms) than controls (4.18 [3.97–4.31] ms, p = 0.034) in the right side. BAEP in the male GI group did not significantly differ from that in controls. GI scores showed a significant correlation with the peak latency of the III wave in the left side (rho = −0.192, p = 0.025). The maternal care PBI scores in the GI group (29 [26]–[33]) were significantly lower than controls (31 [28.5–33], p = 0.010), while the maternal over-protection PBI scores were significantly higher in the GI group (16 [12]–[17]) than controls (13 [10.5–16], p = 0.024). Multiple regression analysis in females also supported these findings.
It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms.
PMCID: PMC3310045  PMID: 22470430
23.  Comparative evaluation of ropivacaine and lignocaine with ropivacaine, lignocaine and clonidine combination during peribulbar anaesthesia for phacoemulsification cataract surgery 
Indian Journal of Anaesthesia  2012;56(1):21-26.
Peribulbar block is the most common type of local anaesthesia administered for cataract surgery, and continuous efforts are on to find a long-acting local anaesthetic (LA) drug with the safest pharmacological profile.
A double-blind, prospective and randomized study was carried out in our institute to compare the anaesthetic effects of ropivacaine with the combination of ropivacaine and clonidine in administration of peribulbar block for phacoemulsification cataract surgery.
A total of 200 patients of both sexes aged 50–80 years of American Society of Anaesthesiologists grade I and II, scheduled for phacoemulsification cataract surgery under monitored anaesthesia care, were enrolled for the study. Patients were assigned into two groups of 100 each; ropivacaine group (R) and ropivacaine clonidine group (RC). Group R received 10 mL of LA solution containing 5 mL of 2% lignocaine, 5 mL of 0.75% ropivacaine and 100 units of hyaluronidase while group RC received 8 mL of a similar mixture with the addition of clonidine 1 μg/kg and saline to make a total volume of 10 mL. Heart rate (HR), mean arterial pressure (MAP), pulse oximetry (SpO2), respiratory rate (RR), intraocular pressure (IOP), eye muscle movement scores and quality of peribulbar block were observed and recorded throughout the study period at regular intervals. At the end of the research project, the data was compiled systematically and was subjected to statistical analysis using the ANOVA test with post hoc significance for continuous variables and Chi-square test for qualitative data. Value of P<0.05 was considered significant and P<0.0001 as highly significant.
Demographic characteristics, SpO2 and RR were comparable in both the groups. Mean HR and MAP were also comparable after a significant variation in the first 2–3 min (P<0.05). Onset and establishment of sensory and motor blocks were significantly earlier in the RC group (P<0.05). IOP decreased significantly during the first 6–7 min in the RC group after the administration of the peribulbar block. Duration of analgesia was prolonged in the RC group (6.5±2.1 h) as compared with the R group (4.2±1.8 h). The side-effect profile revealed a higher incidence of nausea, vomiting, headache and dizziness in Group R, while a considerably higher incidence of dry mouth was observed in Group RC.
Addition of clonidine to ropivacaine not only decreases the total volume of LA to be used but also augments early onset and prolonged offset of sensory analgesia as well as provides smooth operating conditions with a good sedation level as well by providing a wider safety margin of LA.
PMCID: PMC3327065  PMID: 22529415
Cataract; clonidine; peribulbar block; ropivacaine
24.  The use of bispectral analysis to monitor outpatient sedation. 
Anesthesia Progress  2000;47(3):72-83.
The bispectral (BIS) index has been used to interpret partial EEG recordings to predict the level of sedation and loss of consciousness in patients undergoing general anesthesia. The author has evaluated BIS technology in determining the level of sedation in patients undergoing outpatient deep sedation. These experiences are outlined in this review article. Initially, the correlation of the BIS index with traditional subjective patient evaluation using the Observer's Assessment of Alertness and Sedation (OAA/S) scale was performed in 25 subjects. In a second study, the recovery profile of 39 patients where the BIS was used to monitor sedation was compared with a control group where the monitor was not used. A strong positive relationship between the BIS and OAA/S readings was found in the initial subjects. From the recovery study, it appears that use of the BIS monitor may help titrate the level of sedation so that less drugs are used to maintain the desired level of sedation. A trend to earlier return of motor function in BIS-monitored patients was also demonstrated. BIS technology offers an objective, ordinal means of assessing the depth of sedation. This can be invaluable in comparing studies of techniques. The BIS index provides additional information to standard monitoring techniques that helps guide the administration of sedative-hypnotic agents. The trend to earlier return of motor function in BIS-monitored patients warrants further investigation.
PMCID: PMC2149022  PMID: 11432160
25.  Bispectral EEG index monitoring of high-dose nitrous oxide and low-dose sevoflurane sedation. 
Anesthesia Progress  2002;49(2):56-62.
This single-blind controlled clinical study characterized the effects of 30-70% nitrous oxide (N2O) and 0.2-0.8% sevoflurane conscious sedation on quantitative electroencephalographic (EEG) readings of 22 healthy dental students as measured by the bispectral index (BIS). The study verified the 2 previously published BIS/N2O investigations showing no correlation between N2O dosage up to 70% and BIS. Observer's Assessment of Alertness and Sedation scores (OAA/S), however, correlated well with increasing doses of N2O from approximately 35 to 70%. A near linear dose-response relationship was established between OAA/S and end tidal (ET) sevoflurane concentrations of 0.4-0.7%. Only at the highest level of end tidal sevoflurane recorded, 0.7%, was statistically significant BIS depression seen. Subjects evaluated the acceptability of the sedative effect of the 2 gases, showing a slight preference for N2O. Comparable partial anterograde amnesia and sedation (OAA/S) were produced by both agents in administered concentrations of 40-70% N2O and 0.6-0.8% sevoflurane. Female subjects exhibited better memory and significantly less amnesia than males. No statistically significant changes occurred in any of the monitored vital signs. EMG readings demonstrated a statistically significant difference from control values only at the highest, 0.7%, ET concentration of sevoflurane. BIS does not appear useful for evaluating the level of nitrous oxide sedation in the dental setting but may have some value in assessing depth of sedation at deeper levels of sevoflurane sedation.
PMCID: PMC2007394  PMID: 15384293

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