Nebahat Gulcu

Effect of Dexmedetomidine on Ischemia-Reperfusion Injury in Rat Kidney: A Histopathologic Study

Ischemia-reperfusion (I-R) injury remains the leading cause of acute renal failure. The purpose of this experimental study was to determine the role of dexmedetomidine on histologic alterations induced by renal I-R in rats. In the present study, thirty male Sprague-Dawley rats weighing 200–220 g were randomly assigned into three groups: the sham-control group (group 1, n = 10), the R/untreated group (group 2, n = 10), and the I-R/dexmedetomidine-treated group (group 3, n = 10). For group one, we performed a sham operation. The abdomen was dissected, the right kidney was harvested, and then the left renal pedicle exposed. Renal clamping was not applied. For group 2, rats underwent left renal ischemia for 60 minutes followed by reperfusion for 45 minutes. For group 3, the same surgical procedure as in group 2 was performed, and dexmedetomidine (100 μg/kg, intraperitoneal) was administrated at the starting time of reperfusion. The rats were sacrificed after reperfusion, and the kidney tissue was harvested. The histopathological score in the kidney of the I-R/dexmedetomidine-treated group rats was significantly lower than that of I-R/untreated group rats. This score in I-R/untreated group rats was higher than the other two groups, which was statistically significant. In the I-R/untreated group rats, kidneys of untreated ischemia rats showed tubular cell swelling, cellular vacuolization, pyknotic nuclei, medullary congestion, and moderate to severe necrosis. Treatment with dexmedetomidine shows normal glomeruli and slight edema of the tubular cells. These findings provide the first evidence that dexmedetomidine can reduce the renal injury caused by I-R of the kidney, and may be useful in enhancing the tolerance of the kidney against renal injury.

The effects of levobupivacaine versus levobupivacaine plus magnesium infiltration on postoperative analgesia and laryngospasm in pediatric tonsillectomy patients

BACKGROUND The aim of this study was to evaluate whether the addition of magnesium to levobupivacaine will decrease the postoperative analgesic requirement or not, and to investigate the possible preventive effects on laryngospasm. METHODS Seventy-five children undergoing elective tonsillectomy and/or adenoidectomy surgery. The drug was prepared as only NaCl 0.9% for the first group (Group S, n=25), levobupivacaine 0.25% for the second group (Group L, n=25), and levobupivacaine 0.25% plus magnesium sulphate 2mg/kg for the third group (Group M, n=25). Pain was recorded at 15th minute, 1st, 4th, 8th, 16th, and 24th hour postoperatively. Pain was evaluated using a modified Childrens Hospital of Eastern Ontario pain scale (mCHEOPS). Incidence of postoperative nausea and vomiting (PONV) was assessed at various time intervals (0-2, 2-6, 6-24h) by numeric rank score. Patients were followed for laryngospasm for 1h in recovery room after extubation. Other complications appeared within 24h postoperatively were recorded. RESULTS All postoperative CHEOPS values were lower than control in both groups. Analgesic requirement was decreased significantly in both groups in comparison with control patients, but this requirement was significantly lower in Group M (p<0.05). Although laryngospasm was not observed in Group M, the difference between groups was not statistically significant. PONV was similar in both groups. CONCLUSIONS Levobupivacaine and Levobupivacaine plus magnesium infiltration decrease the post-tonsillectomy analgesic requirement. Insignificant preventive effect of low doses of magnesium infiltration on laryngospasm observed in this study needs to be clarified by larger series.

Preconditionin effects of dexmedetomidine on myocardial ischemia/reperfusion injury in rats

BACKGROUND Preconditioning might protect the myocardium against ischemia/ reperfusion injury by reducing infarct size and preventing arrhythmias. Dexmedetomidine (DEX) is a highly selective α2-agonist used for sedoanalgesia in daily anesthetic practice. The cardioprotective effects of DEX on infarct size and on the incidence of arrhythmias observed after regional ischemia/reperfusion injury in vivo have not been reported. OBJECTIVE The aim of this study was to determine whether DEX exhibits a preconditioning effect and reduces infarct size and the incidence and duration of arrhythmias in a regional cardiac ischemia/reperfusion model in rats. METHODS Adult male Sprague-Dawley rats were anesthetized with sodium thiopental and mechanically ventilated (0.9 mL/100 g at 60 strokes/min) through a cannula inserted into the trachea after tracheotomy. Cardiac ischemia was then produced by ligating the left main coronary artery for 30 minutes, followed by a reperfusion period of 120 minutes. Blood pressure (BP) and heart rate (HR) were monitored and echocardiograms (ECGs) were performed. Arrhythmia was scored based on incidence and duration. The animals were randomly divided into 3 groups. The ischemic preconditioning (IPC) group underwent 5 minutes of ischemia followed by 5 minutes of reperfusion before the 30-minute ischemia/120-minute reperfusion period. In the DEX group, intraperitoneal (IP) DEX 1 mL (100 μg/kg) was administered 30 minutes before the ischemia/ reperfusion period. In the control group, IP saline 1 mL was administered 30 minutes before the ischemia/reperfusion period. After reperfusion, the heart was excised, demarcated with saline and ethanol to identify the occluded and nonoccluded myocardium, and cut into slices ~2 mm thick, that were then stained and placed between 2 glass plates. The risk zone and the infarct zone were compared between groups. The investigator assessing the infarcts was blinded to the study group. RESULTS Twenty-one adult (aged 4-6 months) male Sprague-Dawley rats weighing 280 to 360 g were included in the study; 7 rats were assigned to each group. BP, HR, and ECG readings were not significantly different between groups and did not change during the study. Arrythmias occurred during ischemia and reperfusion in all groups. The duration of the arrhythmias was significantly shorter and the arrhythmia score was significantly lower in the IPC group (all, P<0.05), compared with the control group; however, they were not significantly different in the DEX group. During the ischemic period, duration of ventricular tachycardia (VT) and ventricular premature contractions (VPC) in the DEX group was significantly longer than that observed in the IPC group (all, P<0.05). The duration of VPC was also significantly shorter than that observed in the control group (both, P<0.05). Duration of VT during the reperfusion period in the DEX group was significantly longer than that observed in both IPC and control groups (both, P<0.05). The mean (SD) percentage of damage was significantly lower in the IPC group (44.1% [2.0%]) and the DEX group (26.7% [2.0%]) compared with the control group (69.0% [3.0%]; both, P<0.05). The percentage of damage in the DEX group was also significantly lower compared with the IPC group (P<0.05). CONCLUSIONS This small, experimental in vivo study found that DEX was associated with reduced infarct size in ischemia/reperfusion injury in regional ischemia in this rat model but had no effect on the incidence of arrhythmias. Future studies are needed to clarify these findings.

Comparison of dexmedetomidine and midazolam for monitored anesthesia care combined with tramadol via patient-controlled analgesia in endoscopic nasal surgery: A prospective, randomized, double-blind, clinical study

UNLABELLED Abstract. BACKGROUND Monitored anesthesia care (MAC) may be applied for septoplasty or endoscopic sinus surgery in which an adequate sedation and analgesia without respiratory depression are desired for comfort of both the patient and the surgeon. Several combinations with different agents have been used for this purpose in these patients. However, analgesic properties for these agents have not been reported. OBJECTIVE The aim of this study was to investigate the analgesic and sedative effects of dexmedetomidine or midazolam infusion combined with tramadol that was used via patient-controlled analgesia (PCA), and to document the effects of these drugs on early cognitive functions. METHODS This prospective, randomized, double-blind, clinical study enrolled patients undergoing septoplasty or endoscopic sinus surgery at the Abant Izzet Baysal University Hospital, Bolu, Turkey, between February and September 2006. Patients were randomly allocated in a 1:1 ratio into 1 of 2 groups: the dexmedetomidine group (group D) patients received IV dexmedetomidine 1 μg/kg for 10 minutes followed by continuous infusion of 0.5 μg/kg · h(-1); and the midazolam group (group M) patients were administered a loading dose of IV midazolam 40 μg/kg for 10 minutes followed by infusion at the rate of 50 μg/kg · h(-1). A 1-minute bolus dose of IV tramadol (1.5 mg/kg) was administered in both groups 10 minutes after the administration of the primary drug, and continued via infusion using a PCA device. After baseline measurements, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), oxygen saturation, and rate of respiration were recorded after the loading dose of study drug, after the bolus tramadol dose, at 10-minute intervals during the operation, and twice in the recovery rooms; 5 minutes after arrival and 5 minutes before discharge. Verbal rating score (VRS) and Ramsay sedation score were determined at baseline (after surgery was started), every 10 minutes thereafter until the end of the operation, and 2 times during recovery. All patients were assessed with the Wechsler Memory Scale-Revised at baseline (preoperatively) and 4 hours after the operation. RESULTS Seventy patients were enrolled in the study and randomly assigned to 1 of 2 groups: group D (sex, male/female, 23/12; mean [SEM] age, 32.53 [2.07] years; mean [SEM] weight, 73.03 [2.41] kg) or group M (sex, male/female, 21/14; mean [SEM] age, 34.43 [1.83] years; mean [SEM] weight, 67.90 [2.32] kg). All hemodynamic parameters (SAP, DAP, MAP, HR) were significantly higher in group M compared with group D from the onset of the surgery to discharge time (P < 0.05). Pain and sedation scores were similar in both groups, but the amount of PCA-administered rescue tramadol was significantly higher in group M (P = 0.001). A higher, though not statistically significant, prevalence of adverse events (ie, hypotension, bradycardia, and perioperative nausea and vomiting) were observed in group D. Postoperative logical verbal memory and digit span values were significantly higher in group D when compared with group M (P < 0.05). Postoperative digit span and visual reproduction scores were significantly higher than preoperative values in group D (P < 0.05). Postoperative personality functioning scores were significantly higher than preoperative values in group M (P < 0.05). CONCLUSIONS Based on VRS, Ramsay sedation scores, and surgeon and anesthesiologist satisfaction scores, dexmedetomidine or midazolam combined with tramadol PCA provided adequate analgesia and sedation in these adult patients undergoing septoplasty or endoscopic sinus surgery with MAC. A significantly larger amount of rescue tramadol was used by group M, suggesting that a better analgesic effect was achieved with dexmedetomidine.

Oral ketamine for pain relief in a child with abdominal malignancy.

Oral ketamine has been found to be effective during invasive procedures in children with malignancy. To the best of our knowledge, analgesic effects of oral ketamine have not been reported in pediatric cancer pain management. We described a patient with end-stage cancer pain that was resistant to opioids and was relieved by oral ketamine.

Comparison of lidocaine and levobupivacaine in transnasal fiberoptic laryngoscopy.

Background The anatomy of the nasal passages, pharynx, and larynx and evaluation of mucous membranes and laryngeal function is well observed by transnasal fiberoptic laryngoscopy (TFL). In this procedure, to provide good local infiltrative analgesia, medication such as anesthetics is important for the otolaryngologist. The aim of this study was to evaluate the efficacy of lidocaine (L) spray, compared with levobupivacaine solution, used for local anesthetic in patients undergoing TFL for complete examination. Methods Sixty-two subjects (39 men and 23 women; mean age, 36 ± 7 years) were enrolled in the study. Patients were randomly classified into two groups as levobupivacaine hydroclorur (LB) and L groups. A standard flexible transnasal fiberoptic 4.2-mm-diameter laryngoscope was passed through the nasal cavity and into the aerodigestive tract. Patients were asked to evaluate the intensity of the pain they experienced during the TFL, using a visual analog scale (VAS) and Ramsay sedation scale. Results Demographic data were similar in both groups. There was no difference in VAS and Ramsay res between bith groups (p > 0.05). Conclusion Our findings indicated that topical levobupivacaine seems to be an effective medication for anesthesia of the nasal mucosa and may be used to allow complete examinations involving TFL.

The Effect of Prilocaine or Levobupivacaine Infiltration on Pain during Nasal Packing Removal

Objective. The aim of this study was to evaluate the efficacy of rehydration of Merocel nasal packs with prilocaine or levobupivacaine on reducing pain and discomfort of nasal packing removal in patients who had undergone septoplasties or endoscopic sinus surgery. Study Design. Prospective clinical study. Setting. Tertiary referral center. Methods. This prospective study was conducted on 72 patients, aged 18 to 55 years, who had undergone septoplasty, bilateral functional endoscopic sinus surgery, or both. The patients were divided into 2 groups: prilocaine group (group P, n = 36), who received 2.5 mL of 2% prilocaine, and levobupivacaine group (group L, n = 36), who received 2.5 mL of levobupivacaine hydrochloride dilution. These solutions were diluted with 2.5 mL saline to a final volume of 5 mL, which was then injected into the Merocel packing 15 minutes before removal of the pack. In both groups, 5 mL of saline was injected into the packing in the contralateral nostril as a control 15 minutes before removal of the pack. Visual analog score (VAS) and the Ramsay sedation score were recorded. Results. Statistically significant differences were found in VAS and Ramsay sedation scale scores of levobupivacaine and prilocaine groups compared to controls. No significant difference was noted between the groups in terms of levobupivacaine and prilocaine. Conclusions. Levobupivacaine or prilocaine infiltration before removal of nasal packs in patients who undergo septoplasties or endoscopic sinus surgery can decrease discomfort and improve patient tolerability.

Two different doses of caudal neostigmine co-administered with levobupivacaine produces analgesia in children

Background:  This study was aimed to evaluate the analgesic efficacy, duration of analgesia, and side effects of two different doses of caudal neostigmine used with levobupivacaine in children.

Detection of a retained epidural catheter fragment.

To the Editor: We thank the editor for a chance to respond to comments by Drs. Rocco and Philip1 concerning our paper.2 The idea that our study corroborates the findings of Rocco et al.3 is not correct. We measured epidural space pressure as saline was infused at several different flow rates in each animal and found a linear flow-pressure relation with a calculated Y-axis intercept that was within 1 to 2 mm Hg of the actual pressure obtained in the absence of flow. These data argue strongly against the presence of “Starling resistor (SR)” anatomy in the normal pig’s epidural space. If an SR were present, the calculated Y intercept would have been higher than observed, or the relation would have curved down, which indicates recruitment of additional exit pathways with critical opening pressures for fluid leaving the epidural space. In comparison, Rocco et al.3 measured epidural space pressure only at a single flow rate in each patient and, thus, cannot determine whether or not an SR is present. Their best evidence for an SR is the fact that “visible flow” of fluid passively leaving a syringe barrel and entering the epidural space “did not start” until the syringe had been raised some 10 to 15 cm above the spine—not a very scientific approach, because flow rates were not measured and low infusion pressures may have resulted in flow that escaped notice. Thus, the two studies differ in their methods, results, and interpretation. Rocco et al.3 determined their “initial pressure” after infusing small volumes of saline into the epidural space (legend to their Figure 1) and determined their “critical opening pressure” after infusing 3 to 9 mL; hence, to criticize us for doing the same is disingenuous. Their initial pressures were reported as 12 to 15 mm Hg, but these numbers come from only 13 of 25 patients studied. What were the pressures in the other 12 patients, and why were they excluded from analysis? Of additional note, the technique used by Rocco et al.3 for calculating “pressure at zero flow” was invalid because they extrapolated epidural space pressure versus time, rather than versus flow. On the other hand, we are pleased to note the similarity between our Figure 1 and their Figure 4, a tracing of pressure recorded during constant-flow volume infusion in an apparently healthy patient scheduled for surgery. The feature that is common to the two figures is a plateau in epidural space pressure as flow continues. We believe this plateau means that saline leaves the epidural space through pathways with constant resistance and enters a system with large capacitance. Otherwise, pressure would continue to increase rather than plateau. Our study was done in normal pigs, and finding similar results in a human is encouraging. Rocco et al.3 think certain technical aspects of our study precluded demonstration of SR-type hydrodynamic behavior. The linearity of our flow-pressure relations (R2 0.98 1.0) means that extrapolation to determine the Y-axis intercept is reasonable and accurate; hence, we would have found evidence of a critical opening pressure had it been present. The linearity of the relation adequately rules out recruitment of additional pathways with higher opening pressures as well. Rocco et al.3 are correct that infused fluid needs to reach the pressure-sensing needle before a reliable measurement can be made, but this distance was only 2 to 3 cm in our study because the needles were located at adjacent interspaces. They miss the bigger picture, however, which is that fluid spreads up and down the epidural space and through a variety of exit pathways, all of which might well demonstrate SR behavior. Rocco et al.3 confuse terms when they state that “once the critical opening pressure (initial pressure) is reached. . .” We strongly disagree with the concept that pressure measured in the absence of flow (initial pressure) corresponds to a critical opening pressure, and Rocco et al.3 make this distinction in Table 2 of their previous publication. Frankly, we were surprised to observe a pressure plateau during fluid infusion and that our flow-pressure relations were linear. We think the situation is more analogous to the flow of saline into a vein than into a “space” with limited capacitance and run off. Further studies are necessary to determine the location and nature of the exit pathways from the spinal epidural space that influence the hydrodynamics we have observed.

A Lateral Percutaneous Technique for Stellate Ganglion Blockade in Rats

BACKGROUND: In the present study, we describe and show the efficacy of a lateral approach to stellate ganglion block (SGB) in rats. METHODS: Twenty-one rats were randomized into three groups: the posterior technique group (n = 7), the lateral technique group (n = 7), and the control group (n = 7). Thiopental was administered intraperitonally as 5 mg per 100 g of each rats weight for sedation during the procedure. In the posterior technique group, SGB was performed by a posterior percutaneous approach as described previously. In the lateral technique and control groups, the cervical vertebrae was fixed between the left first and third fingers of the physicians left hand while palpating the C7 process with the second finger. The study drug was 0.2 mL 0.25% plain bupivacaine for the two percutaneous treatment groups, and 0.2 mL saline in the controls. RESULTS: Two animals in the posterior technique group died immediately after local anesthetic injection (P < 0.01). There were no deaths in the new technique group or in the controls. Ptosis appeared at 300 ± 120 s in the posterior group, whereas it was seen almost immediately after withdrawing the needle in the lateral technique group (6 ± 4 s) (P < 0.001). Ptosis did not occur in the control group. There was no statistically significant difference in heart rate among groups (P > 0.069). CONCLUSION: The lateral approach to SGB does not require the induction of general anesthesia. The approach is associated with early development of ptosis and may be associated with a lower mortality rate compared to the conventional posterior approach.