Effects of warmed carrier fluid on nefopam injection-induced pain.

BACKGROUND: Nefopam is a non-opioid, non-steroidal analgesic drug with fewer adverse effects than narcotic analgesics and nonsteroidal anti-inflammatory drugs, and is widely used for postoperative pain control. Because nefopam sometimes causes side effects such as nausea, vomiting, somnolence, hyperhidrosis and injection-related pain, manufacturers are advised to infuse it slowly, over a duration of 15 minutes. Nevertheless, pain at the injection site is very common. Therefore, we investigated the effect of warmed carrier fluid on nefopam injection-induced pain. METHODS: A total of 48 patients were randomly selected and allocated to either a control or a warming group. Warming was performed by diluting 40 mg of nefopam in 100 ml of normal saline heated to 31-32℃ using two fluid warmers. The control group was administered 40 mg of nefopam dissolved in 100 ml of normal saline stored at room temperature (21-22℃) through the fluid warmers, but the fluid warmers were not activated. RESULTS: The pain intensity was lower in the warming group than in the control group (P < 0.001). The pain severity and tolerance measurements also showed statistically significant differences between groups (P < 0.001). In the analysis of vital signs before and after the injection, the mean blood pressure after the injection differed significantly between the groups (P = 0.005), but the heart rate did not. The incidence of hypertension also showed a significant difference between groups (P = 0.017). CONCLUSIONS: Use of warmed carrier fluid for nefopam injection decreased injection-induced pain compared to mildly cool carrier fluid.

Effects of nefopam on catheter-related bladder discomfort in patients undergoing ureteroscopic litholapaxy.

BACKGROUND: Patients who undergo urinary catheterization may experience postoperative catheter-related bladder discomfort (CRBD). Previous studies have indicated that drugs with antimuscarinic effects could reduce the incidence and severity of CRBD. Accordingly, this study was carried out to investigate whether nefopam, a centrally acting analgesic with concomitant antimuscarinic effect, reduces the incidence and severity of CRBD. METHODS: Sixty patients with American Society of Anesthesiologists physical status I and II and aged 18-70 years who were scheduled to undergo elective ureteroscopic litholapaxy participated in this double-blinded study. Patients were divided into control and nefopam groups, comprising 30 patients each. In the nefopam group, 40 mg nefopam in 100 ml of 0.9% saline was administered intravenously. In the control group, only 100 ml of 0.9% saline was administered. All patients had a urethral catheter and ureter stent inserted during surgery. The incidence and severity of CRBD, numerical rating scale (NRS) score of postoperative pain, rescue pethidine dose, and side effects were recorded in the post-anesthesia care unit after surgery. RESULTS: The incidence (P = 0.020) and severity (P < 0.001) of CRBD were significantly different between the control group and the nefopam group. The NRS score of postoperative pain (P = 0.006) and rescue dose of pethidine (P < 0.001) were significantly higher in the control group than in the nefopam group. CONCLUSIONS: Intravenous administration of nefopam in patients scheduled to undergo ureteroscopic litholapaxy reduced the incidence and severity of CRBD, NRS score of postoperative pain and analgesic requirements.

Effects of glycopyrrolate premedication on preventing postoperative catheter-related bladder discomfort in patients receiving ureteroscopic removal of ureter stone.

BACKGROUND: Glycopyrrolate given as reversing agents of muscle relaxants has been reported to be effective in reducing postoperative catheter-related bladder discomfort (CRBD). However, it remains unclear whether glycopyrrolate as premedication is also effective. This study aims to investigate the effectiveness of glycopyrrolate as premedication on preventing CRBD in the post-anesthesia care unit (PACU). METHODS: Eighty-three patients who received elective ureteroscopic removal of ureteral stone were randomly assigned to the control (n = 43) or the glycopyrrolate group (n = 40). The glycopyrrolate group was treated with glycopyrrolate 0.3 mg as premedication while the control group received 0.9% saline 1.5 ml. The incidence and severity of CRBD and pain score using numerical rating scale (NRS) were measured in the PACU. RESULTS: The incidence of CRBD (26 of 40 patients vs. 41 of 43 patients, relative risk [RR] = 0.68, 95% Confidence interval [CI] = 0.53-0.86, P = 0.001) and the moderate to severe CRBD incidence (6 of 40 patients vs. 20 of 43 patients, RR = 0.32, 95% CI = 0.14-0.72, P = 0.002) were lower in the glycopyrrolate group than in the control group. Also, postoperative pain NRS score was found to be lower in the glycopyrrolate group (median = 1 [Q1 = 0, Q3 = 2]) compared to the control group (3 [1, 5], median difference = 1.00, 95% CI = 0.00-2.00, P = 0.002). CONCLUSIONS: The use of glycopyrrolate 0.3 mg as premedication in patients receiving ureteroscopic removal of ureteral stone reduced the incidence and severity of CRBD, and decreased postoperative pain in the PACU.

The correlation between the Trendelenburg position and the stroke volume variation.

BACKGROUND: The stroke volume variation (SVV), based on lung-heart interaction during mechanical ventilation, is a useful dynamic parameter for fluid responsiveness. However, it is affected by many factors. The aim of this study was to evaluate the effects of SVV on Trendelenburg (T) and reverse Trendelenburg (RT) position and to further elaborate on the patterns of the SVV with position. METHODS: Forty-two patients undergoing elective surgery were enrolled in this study. Fifteen minutes after standardized induction of anesthesia with propofol, fentanyl, and rocuronium with volume controlled ventilation (tidal volume of 8 ml/kg of ideal body weight, inspiration : expiration ratio of 1 : 2, and respiratory rate of 10-13 breaths/min), the patients underwent posture changes as follows: supine, T position at slopes of operating table of -5°, -10°, and -15°, and RT position at slopes of operating table of 5°, 10°, and 15°. At each point, SVV, cardiac output (CO), peak airway pressure (PAP), mean blood pressure, and heart rate (HR) were recorded. RESULTS: The SVV was significant decreased with decreased slopes of operating table in T position, and increased with increased slopes of operating table in RT position (P = 0.000). Schematically, it was increased by 1% when the slope of operating table was increased by 5°. But, the CO and PAP were significant increased with decreased slopes of operating table in T position, and decreased with increased slopes of operating table in RT position (P = 0.045, 0.027). CONCLUSIONS: SVV is subjected to the posture, and we should take these findings into account on reading SVV for fluid therapy.

CO2 relaxation of the rat lung parenchymal strip.

Evidence from liquid-filled rat lungs supported the presence of CO2-dependent, active relaxation of parenchyma under normoxia by unknown mechanisms (Emery et al., 2007). This response may improve matching of alveolar ventilation (V˙A) to perfusion (Q˙) by increasing compliance and V˙A in overperfused (high CO2) regions, and decrease V˙A in underperfused regions. Here, we have more directly studied CO2-dependent parenchymal relaxation and tested a hypothesized role for actin-myosin interaction in this effect. Lung parenchymal strips (∼1.5mm×1.5mm×15mm) from 16 rats were alternately exposed to normoxic hypocapnia ( [Formula: see text] ) or hypercapnia ( [Formula: see text] ). Seven specimens were used to construct length-tension curves, and nine were tested with and without the myosin blocker 2,3-butanedione monoxime (BDM). The results demonstrate substantial, reversible CO2-dependent changes in parenchyma strip recoil (up to 23%) and BDM eliminates this effect, supporting a potentially important role for parenchymal myosin in V˙A/Q˙ matching.

A comparative study of emergence agitation between sevoflurane and propofol anesthesia in adults after closed reduction of nasal bone fracture.

BACKGROUND: Emergence agitation is associated with increased morbidity and hospital costs. However, there have been few reports in the medical literature on the occurrence of emergence agitation in adults. The aim of this study was to compare emergence agitation between sevoflurane and propofol anesthesia in adults after closed reduction of nasal bone fracture. METHODS: Forty adults (ASA I-II, 20-60 yr) undergoing closed reduction of nasal bone fracture were randomly assigned to either sevoflurane or propofol group and anesthesia was maintained with sevoflurane or propofol. The bispectral index (BIS) was monitored and maintained within 40-60. At the end of surgery, patients were transported to the post anesthetic care unit (PACU) and agitation state scale was checked by Aono's four-point scale (AFPS). Emergence agitation was defined as and AFPS score of 3 or 4. Pain score were measured by numeric rating scale (NRS) on arrival and peak value at PACU. RESULTS: Nine (45.0%) patients in the sevoflurane group and 2 (10.0%) patients in the propofol group developed emergence agitation in the PACU (P = 0.031). There was no correlation between peak NRS and Aono's four-point scale. CONCLUSIONS: Propofol may decrease incidence of emergence agitation compared to sevoflurane in adults undergoing closed reduction of nasal bone fracture.

The Effects of Postoperative Brachial Plexus Block Using MgSO(4) on the Postoperative Pain after Upper Extremity Surgery.

BACKGROUND: Although a brachial plexus block can be used to provide anesthesia and analgesia for upper extremity surgery, its effects using MgSO(4) on postoperative pain management have not been reported. The aim of this study was to evaluate brachial plexus block using MgSO(4) on postoperative analgesia. METHODS: Thirty-eight patients who were scheduled to undergo upper extremity surgery were randomly allocated into two groups: patients receiving axillary brachial plexus block with 0.2% ropivacaine 20 ml and normal saline 2 ml (group S) or 0.2% ropivacaine 20 ml and MgSO(4) 200 mg (group M). Before extubation, the blocks were done and patient controlled analgesia was started, and then, the patients were transported to a postanesthetic care unit. The postoperative visual analogue scale (VAS), opioid consumption, and side effects were recorded. RESULTS: The two groups were similar regarding the demographic variables and the duration of the surgery. No differences in VAS scores were observed between the two groups. There was no statistically significant difference in opioid consumption between the two groups. Nausea was observed in three patients for each group. CONCLUSIONS: Axillary brachial plexus block using MgSO(4) did not reduce the level of postoperative pain and opioid consumption.

Remifentanil-induced pronociceptive effect and its prevention with pregabalin.

BACKGROUND: Experimental and clinical studies have suggested that remifentanil probably causes acute tolerance or postinfusion hyperalgesia. This study was designed to confirm whether remifentanil given during propofol anesthesia induced postoperative pain sensitization, and we wanted to investigate whether pregabalin could prevent this pronociceptive effect. METHODS: Sixty patients who were scheduled for total abdominal hysterectomy were randomly allocated to receive (1) a placebo as premedication and an intraoperative saline infusion (control group), (2) a placebo as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (remifentanil group), or (3) pregabalin 150 mg as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (pregabalin-remifentanil group). Postoperative pain was controlled by titration of fentanyl in the postanesthetic care unit (PACU), followed by patient-controlled analgesia (PCA) with fentanyl. The patients were evaluated using the visual analogue scale (VAS) for pain scores at rest and after cough, consumption of fentanyl, sedation score and any side effects that were noted over the 48 h postoperative period. RESULTS: The fentanyl titration dose given in the PACU was significantly larger in the remifentanil group as compared with those of the other two groups. At rest, the VAS pain score in the remifentanil group at 2 h after arrival in the PACU was significantly higher than those in the other two groups. CONCLUSIONS: The results of this study show that remifentanil added to propofol anesthesia causes pain sensitization in the immediate postoperative period. Pretreatment with pregabalin prevents this pronociceptive effect and so this may be useful for the management of acute postoperative pain when remifentanil and propofol are used as anesthetics.

The effect of milrinone infusion on right ventricular function during coronary anastomosis and early outcomes in patients undergoing off-pump coronary artery bypass surgery.

BACKGROUND: During coronary anastomosis in off-pump coronary artery bypass surgery (OPCAB), hemodynamic alternations can be induced by impaired diastolic function of the right ventricle. This study was designed to examine the effect of milrinone on right ventricular function and early outcomes in patients undergoing OPCAB. METHODS: Forty patients undergoing OPCAB were randomly assigned in a double-blind manner to receive either milrinone (milrinone group, n = 20) or normal saline (control group, n = 20). Hemodynamic variables were measured after pericardiotomy (T1), 5 min after stabilizer application for anastomosis of the left anterior descending coronary artery (LAD, T2), the obtuse marginalis branch (OM, T3), the right coronary artery (RCA, T4), 5 min after sternal closure (T5), and after ICU arrival. The right ventricular ejection fraction (RVEF) and right ventricular volumetric parameters were also measured using the thermodilution technique. For evaluation of early outcomes, the 30-day operative mortality and morbidity risk models were used. RESULTS: There was no significant difference in hemodynamic variables, including mean arterial pressure, between the 2 groups, except for the cardiac index and RVEF. The cardiac index and RVEF were significantly greater at T3 in the milrinone group than in the control group. CONCLUSIONS: Continuous infusion of milrinone demonstrated a beneficial effect on cardiac output and right ventricular function in patients undergoing OPCAB, especially during anastomosis of the graft to the OM artery, and it had no adverse effect on early outcomes.

Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine.

The amphetamine derivative (+/-)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliative emotional response. MDMA is a potent monoaminergic neurotoxin with the potential to damage brain serotonin and/or dopamine neurons. As the majority of MDMA users are young adults, the risk that users may expose the fetus to MDMA is a concern. However, the majority of studies on MDMA have investigated the effects on adult animals. Here, we investigated whether long-term exposure to MDMA, especially in adolescence, could induce comprehensive transcriptional changes in mouse brain. Transcriptomic analysis of mouse brain regions demonstrated significant gene expression changes in the cerebral cortex. Supervised analysis identified 1028 genes that were chronically dysregulated by long-term exposure to MDMA in adolescent mice. Functional categories most represented by this MDMA characteristic signature are intracellular molecular signaling pathways of neurotoxicity, such as, the MAPK signaling pathway, the Wnt signaling pathway, neuroactive ligand-receptor interaction, long-term potentiation, and the long-term depression signaling pathway. Although these resultant large-scale molecular changes remain to be studied associated with functional brain damage caused by MDMA, our observations delineate the possible neurotoxic effects of MDMA on brain function, and have therapeutic implications concerning neuro-pathological conditions associated with MDMA abuse.

The effects of lidocaine and fentanyl on airway irritability during inhalation induction with desflurane.

BACKGROUND: Inhalation induction with desflurane can cause airway irritability and sympathetic stimulation. The aim of this study was to investigate whether lidocaine and fentanyl could reduce these unwanted reactions. METHODS: Seventy-five patients who had premedication with midazolam were randomly allocated to one of three groups to receive intravenous saline (S group), lidocaine 1.5 mg/kg (L group), fentanyl 1 microgram/kg (F group), respectively, before tidal volume induction with desflurane in oxygen and nitrous oxide. We recorded airway irritability such as cough, apnea, laryngospasm and excitatory movement and hemodynamic changes. RESULTS: Airway irritability was not significantly different between the groups. In F group, mean blood pressure at LOC ver and LOC BIS and heart rate at LOC ver, LOC BIS and just before intubation were lower than those of S group (P < 0.05). Other results were not significantly different. CONCLUSIONS: The results of the study showed that intravenous fentanyl and lidocaine had no beneficial effects to reduce airway irritability, but intravenous fentanyl could significantly reduce hemodynamic stimulation during inhalation induction with desflurane in the patients who were premedicated with midazolam.

Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by nitrite in isolated, perfused rat lungs.

Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect of nitrite on the pulmonary circulation has not been well characterized. We explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated vasodilation. As to method, isolated rat lungs were perfused with buffer, or buffer with RBCs, and subjected to repeated hypoxic challenges, with or without nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite concentrations of 7 muM and above. Nitrite inhibition of HPV was prevented by excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO. Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition of HPV by nitrite (maximum nitrite concentration of approximately 35 muM) independent of perfusate Po(2). Degradation of nitrite was accelerated by hypoxia in the presence of RBCs but not during buffer perfusion. In conclusion, low micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and when RBC concentration is subphysiological. This effect is lost when RBC concentration approaches physiological levels, despite enhanced nitrite degradation in the presence of RBCs. These data suggest that, although deoxyHb may generate NO from nitrite, insufficient NO escapes the RBC to cause vasodilation in the pulmonary circulation under the dynamic conditions of blood flow through the lungs and that RBCs are net scavengers of NO.

Pulmonary vascular effects of red blood cells containing S-nitrosated hemoglobin.

The role of S-nitrosated hemoglobin (SNO-Hb) in the regulation of blood flow is a central and controversial question in cardiopulmonary physiology. In the present study, we investigate whether intact human red blood cells (RBCs) synthesized to contain high SNO-Hb levels are able to export nitric oxide bioactivity and vasodilate the pulmonary circulation, and whether SNO-Hb dependent vasodilation occurs secondary to an intrinsic oxygen-linked, allosteric function of Hb. RBCs containing supraphysiological concentrations (100-1,000x normal) of SNO-Hb (SNO-RBCs) were synthesized and added to isolated, perfused rat lungs during anoxic or normoxic ventilation, and during normoxic ventilation with pulmonary hypertension induced by the thromboxane mimetic U-46619. SNO-RBCs produced dose-dependent pulmonary vasodilation compared with control RBCs during conditions of both normoxic (U-46619) and hypoxic pulmonary vasoconstriction. These effects were associated with a simultaneous, rapid, and temperature-dependent loss of SNO from Hb. Both vasodilatory effects and the rate of SNO-Hb degradation were independent of oxygen tension and Hb oxygen saturation. Furthermore, these effects were not affected by inhibition of the RBC membrane band 3 protein (anion exchanger-1), a putative membrane facilitator of NO export from RBCs. Whereas these data support observations by multiple groups that synthesized SNO-Hb can vasodilate, this effect is not under intrinsic oxygen-dependent allosteric control, nor likely to be relevant in the pulmonary circulation at normal physiological concentrations.