Effect of remifentanil preconditioning on myocardial ischemia-reperfusion injury / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the delayed cardioprotection induced by remifentanil in intact rat ischemia-reperfusion (I/R) models.</p><p><b>METHODS</b>Totally 42 adult male Wistar rats weighing 200-300 g were randomly divided into 7 groups (n = 6 in each group): In Group I, rats were injected with normal saline via tail vein, performed with the regimen of 3 x 5-min intravenous (i.v.) infusion at a rate of 0.1 ml x kg(-1) min(-1) 24 h before I/R; In Group II, rats were treated according to the same experimental protocols as in Group I except receiving additional naloxone (0.1 mg/kg) 10 minutes before normal saline pretreatment; In Groups III, IV, V, and VI, rats were treated with remifentanil via tail vein, performed with the regime of 3 x 5-min i.v. infusion at a rate of 2 microg x kg(-1) x min(-1) 12 h, 24 h, 48 h, and 72 h before I/R; In Group VII, the rats were treated according to the same experimental protocols as in Group IV except that they received additional naloxone (0.1 mg/kg) 10 minutes before remifentanil pretreatment. Heart rate (HR), mean arterial pressure (MAP), and a lead II electrocardiogram were continuously monitored during IR process. To determine plasma concentration of creatine kinase myocardial isoenzyme-MB (CK-MB), arterial blood samples were obtained immediately before ischemia, and at the end of ischemia and reperfusion. After a 120-min reperfusion, heart was removed for the measurement of myocardial infarct size. Infarct size (IS) was expressed as percentage of the area at risk.</p><p><b>RESULTS</b>HR, MAP, and rate-pressure product were not significantly different at each time points among all groups (P > 0.05). Compared with Group I, plasma concentrations of CK-MB at the end of ischemia and reperfusion and myocardial infarct size were significantly lower in Groups IV and V (P < 0.05). Compared with Group IV, plasma concentrations of CK-MB at the end of ischemia and reperfusion were significantly higher and myocardial infarct size was significantly larger in Group VII (P < 0.05).</p><p><b>CONCLUSION</b>Remifentanil preconditioning induces delayed cardioprotection in intact rat ischemia-reperfusion model, which may be triggered via opioid receptors.</p>

Median effective dose of remifentanil for awake laryngoscopy and intubation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Awake intubation requires an anesthetic management that provides sufficient patient safety and comfort, adequate intubating conditions, and stable hemodynamics. In this prospective clinical study, our aim was to determine the median effective dose (ED(50)) of remifentanil in combination with midazolam and airway topical anesthesia for awake laryngoscopy and intubation.</p><p><b>METHODS</b>Thirty-six female adult patients, scheduled for elective plastic surgery under general anesthesia requiring orotracheal intubation were included in this study. Ten minutes after intravenous administration of midazolam 0.1 mg/kg, patients were assigned to receive remifentanil in bolus, followed by a continuous infusion. The bolus dose and infusion rate of remifentanil were adjusted by a modified Dixon's up-and-down method. Patient's reaction score at laryngoscopy and an Observer's Assessment of Alertness/Sedation Scale (OAA/S) were used to determine whether the remifentanil dosage regimen was accepted. During laryngoscopy, 2% lidocaine was sprayed into the airway to provide the topical anesthesia. ED(50) of remifentanil was calculated by the modified Dixon up-and-down method, and the probit analysis was then used to confirm the results obtained from the modified Dixon's up-and-down method. In the patients who were scored as "accept", patient's OAA/S and reaction scores at different observed points, intubating condition score and patient's tolerance to the endotracheal tube after intubation were evaluated and recorded. Blood pressure and heart rate at different measuring points were also noted.</p><p><b>RESULTS</b>ED(50) of remifentanil for awake laryngoscopy and intubation obtained by the modified Dixon's up-and-down method was (0.62 +/- 0.02) microg/kg. Using probit analysis, ED(50) and ED(95) of remifentanil were 0.63 microg/kg (95% CI, 0.54 - 0.70) and 0.83 microg/kg (95% CI, 0.73 - 2.59), respectively. Nineteen patients who were scored as "accept" had an OAA/S of > 15 and tolerated well laryngoscopy without significant discomfort or gagging. The mean intubating condition score was 1.8 +/- 0.8. The endotracheal tube was well tolerated. During awake laryngoscopy and intubation, blood pressure and heart rate were also kept stable. The postoperative follow up showed that no patient recalled discomfort and pain for airway manipulation.</p><p><b>CONCLUSIONS</b>When combined with midazolam 0.1 mg/kg and airway topical anesthesia, ED(50) of remifentanil for successful awake laryngoscopy and intubation is 0.62 microg/kg in bolus followed by continuous infusion of 0.062 microg*kg(-1)*min(-1). This sedation and analgesia regimen can provide patient safety and comfort, ensure adequate intubating conditions, maintain hemodynamic stability, and prevent negative recall of the airway procedure.</p>

Clinical assessment of awake endotracheal intubation using the lightwand technique alone in patients with difficult airways / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There is few study to determine whether the use of the lightwand technique alone could achieve effective, safe and successful awake endotracheal intubation (ETI), therefore we designed a prospective clinical study to systematically evaluate the feasibility, safety and efficacy of awake ETI using the lightwand alone in patients with difficult airways.</p><p><b>METHODS</b>Seventy adult patients with difficult airways were enrolled in this study. After the desired sedation with fentanyl and midazolam, airway topical anesthesia was performed with 9 ml of 2% lidocaine, which were in order sprayed in three aliquots at 5 minutes intervals into the supraglottic (two doses) and laryngotracheal areas (one dose) using a combined unit of the lightwand and MADgic atomizer. After airway topical anesthesia, awake ETI was performed using a Lightwand. Subjective assessments by patients and operators using the visual analogue scores (VAS), and objective assessments by an independent investigator using patients' tolerance and reaction scores, coughing severity, intubating conditions and cardiovascular variables were taken as the observed parameters.</p><p><b>RESULTS</b>Of 210 airway sprays, 197 (93.8%) were successfully completed on the first attempt. The total time for airway spray was (14.6 +/- 1.5) minutes. During airway topical anesthesia, the average patients' tolerance scores were 1.7 - 2.3. After airway topical anesthesia, the mean VAS for discomfort levels that the patients reported was 6.5. Also airway topical anesthesia procedure was rated as acceptable and no discomfort by 94.3% of patients. The lightwand-guided awake ETI was successfully completed on first attempt within 29 seconds in all patients. During awake ETI, patients' reaction and coughing scores were 1.9 and 1.6, respectively. All patients exhibited excellent or acceptable intubating conditions. Cardiovascular monitoring revealed that changes of systolic blood pressure and heart rate at each stage of airway manipulations were less than 20% of baseline values. The postoperative follow-up showed that 95.7% of patients had no recall or slight memories of all airway instrumentation. The incidence of postoperative mild airway complications was 38.6%.</p><p><b>CONCLUSION</b>Alone use of the lightwand technique can achieve effective, safe and successful awake ETI in patients with difficult airways.</p>

Comparison of bolus remifentanil versus bolus fentanyl for blunting cardiovascular intubation responses in children: a randomized, double-blind study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The authors found no study to compare the efficacy of bolus dose fentanyl and remifentanil blunting the cardiovascular intubation response in children, so they designed this randomized, double-blind clinical study to assess the effects of remifentanil 2 microg/kg and fentanyl 2 microg/kg by bolus injection on the cardiovascular intubation response in healthy children.</p><p><b>METHODS</b>One hundred and two children, the American Society of Anesthesiologists (ASA) physical status 1-2 and scheduled for elective plastic surgery under general anesthesia, were randomly divided into one of two groups to receive the following treatments in a double blind manner: remifentanil 2 microg/kg (Group R) and fentanyl 2 microg/kg (Group F) when anesthesia was induced with propofol and vecuronium. The orotracheal intubation was performed using a direct laryngoscope. Blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline values), immediately before intubation, at intubation and every minute for 5 minutes after intubation. The percent changes of systolic blood pressure (SBP) and HR relative to baseline values and the rate pressure product (RPP) at every observing point were calculated. The incidences of SBP and HR percent changes >30% of baseline values and RPP >22,000 during the observation were recorded.</p><p><b>RESULTS</b>There were no significant differences between groups in the demographic data, baseline values of BP and HR and the intubation time. As compared to baseline values, BP, HR and RPP at intubation and their maximum values during observation increased significantly in Group F, but they all decreased significantly in Group R. BP, HR and RPP at all observed points, and their maximum values during the observation, were significantly different between groups. There were also significant differences between groups in the percent change of SBP and HR relative to baseline values at all observed points and their maximum percent changes during the observation. The incidences of SBP and HR percent increased >30% of the baseline values and RPP >22,000 during the observation, were significantly higher in Group F than in Group R, but the incidences of SBP and HR percent decreased >30% of baseline values were significantly lower in Group F compared with Group R.</p><p><b>CONCLUSIONS</b>When used as part of routine anesthesia induction with propofol and vecuronium in children, fentanyl 2 microg/kg by bolus injection fails to effectively depress the cardiovascular intubation response. Remifentanil 2 microg/kg by bolus injection can completely abolish the cardiovascular intubation response, but also cause more adverse complications of temporary significant cardiovascular depression.</p>

Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.</p><p><b>METHODS</b>The hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n = 10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) and L-NAME (100 micromol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment. The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.</p><p><b>RESULTS</b>The cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1, the cardiac function variables and coronary flow at all the observed points were significantly improved in Group 2. The cardiac function variables and coronary flow were better in Group 3 than in Group 1, but were inferior in Group 3 than in Group 2. Both NO contents and NOS activity in the myocardium were significantly higher in Group 2 than in Group 1. However, NOS contents in the myocardium did not significantly differ between Groups 1 and 2.</p><p><b>CONCLUSIONS</b>In isolated rat hearts, propofol can improve cardiac functional recovery after ischemia-reperfusion by upregulating NOS activity in the myocardium. The NO system may play an important role in the preservation of myocardial ischemia-reperfusion injury produced by propofol.</p>

Circulatory responses to nasotracheal intubation: comparison of GlideScope videolaryngoscope and Macintosh direct laryngoscope / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The GlideScope videolaryngoscope (GSVL) has been shown to have no special advantage over the Macintosh direct laryngoscope (MDL) in attenuating the circulatory responses to orotracheal intubation, but no study has compared the circulatory responses to nasotracheal intubation (NTI) using the two devices. This prospective randomized clinical study was designed to determine whether there was a clinically relevant difference between the circulatory responses to NTI with the GSVL and the MDL.</p><p><b>METHODS</b>Seventy-six adult patients were randomly allocated equally to the GSVL group and the MDL group. After induction of anesthesia, NTI was performed. Non-invasive blood pressure (BP) and heart rate (HR) were recorded before induction (baseline values) and immediately before intubation (post-induction values), at intubation and every minute for a further five minutes. During the observation, times required to reach the maximum values of systolic BP (SBP) and HR, times required for recovery of SBP and HR to postinduction values and incidence of SBP and HR percent changes > 30% of baseline values were also noted. The product of HR and systolic BP, i.e. rate pressure product (RPP), and the areas under SBP and HR vs. time curves (AUC(SBP) and AUC(HR)) were calculated.</p><p><b>RESULTS</b>The NTI with the GSVL resulted in significant increases in BP, HR and RPP compared to postinduction values, but these circulatory changes did not exceed baseline values. BPs at all measuring points, AUC(SBP), maximum values of BP and incidence of SBP percent increase > 30% of baseline value during the observation did not differ significantly between groups. However, HR and RPP at intubation and their maximum values, AUC(HR) and incidence of HR percent increase > 30% of baseline value were significantly higher in the MDL group than in the GSVL group. Times required for recovery of SBP and HR to postinduction values were significantly longer in the MDL group than in the GSVL group.</p><p><b>CONCLUSIONS</b>The pressor response to NTI with the GSVL and the MDL was similar, but the tachycardiac response to NTI was lesser and of a shorter duration when using a GSVL than when using an MDL.</p>

Clinical experience of airway management and tracheal intubation under general anesthesia in patients with scar contracture of the neck / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Because patients with scar contracture of the neck are at a high risk of loss of the airway control after anesthesia induction, awake intubation is usually recommended. This retrospective clinical study was designed to evaluate the possibility, safety and efficacy of airway management and tracheal intubation under general anesthesia in such patients.</p><p><b>METHODS</b>This retrospective study included 1683 patients from January 1994 to December 2006 with scar contracture of the neck, aged 1.5 - 67.0 years, who were scheduled for elective plastic surgery under general anesthesia in Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Based on the results of the preoperative airway assessment, the patients were classified into group 1 (including 1375 patients with the atlanto-occipital extension of > 20 degrees and the Mallampatti's grade I or II) and group 2 (containing 308 patients with the atlanto-occipital extension of < 20 degrees and the Mallampatti's grade III or IV. In group 1, the intravenous induction and maintenance of anesthesia and succinylcholine for muscle relaxation were used. The intubation was done using a modified Macintosh technique. In group 2, the total intravenous anesthesia (TIVA) or the sevoflurane inhalation anesthesia was chosen and the spontaneous breathing was reserved during anesthesia. The intubation was performed by a fiberoptic stylet laryngoscope (FOSL). The number of intubation attempts, intubation time and relative complications were observed and recorded in all patients.</p><p><b>RESULTS</b>In group 1, the intubation was accomplished during the first attempt in 1279 cases (93%) and the intubation time was < 3 minutes in 1304 cases (95%). In group 2, the intubation was completed by the first attempt in 114 patients (37%) and 123 patients had an intubation time of < 3 minutes (40%). Tracheal intubation was successful by the second or third attempt in 96 patients in group 1 and 156 patients in group 2. Thirty-eight patients required four or more attempts which only occurred in group 2. The incidence of traumatic complication was 2.6% and 9.7% with one intubation attempt in groups 1 and 2, respectively, 12.5% and 17.0% with multiple intubation attempts (one vs multiple attempts in both groups, P < 0.001). All non-traumatic complications occurred in group 2 and laryngospasm and hypoxemia were more common in patients using the TIVA compared to those using the sevoflurane inhalational anesthesia (P < 0.001).</p><p><b>CONCLUSIONS</b>This study demonstrated that with a precise airway evaluation, an adequate preoperative preparation and a pre-planned failed intubation strategy, the anesthetist who was experienced in the difficult airway management could safely perform airway control and tracheal intubation under general anesthesia in patients with scar contracture of the neck. We believe that this technique may be very valuable for the management of a known difficult airway because it is comfortable for the patient and saves time for the anesthetist.</p>

Comparison of hemodynamic responses to nasotracheal intubations with Glide Scope video-laryngoscope, Macintosh direct laryngoscope, and fiberoptic bronchoscope / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the hemodynamic responses to nasotracheal intubation with Glide Scope video-laryngoscope (GSVL), Macintosh direct laryngoscope (MDLS), and fiberoptic bronchoscope (FOB).</p><p><b>METHODS</b>Sixty patients, with American Society of Anesthesiologists (ASA) physical status I - II, aged 18- 50 years, and scheduled for elective plastic surgery under general anesthesia requiring nasotracheal intubation, were randomly allocated equally to GSVL group, MDLS group, and FOB group. After the routine anesthesia induction, nasotracheal intubation was performed with the GSVL, MDLS, and FOB, respectively. Noninvasive blood pressure (BP) and heart rate (HR) were recorded before (baseline values) and after anesthesia induction (postinduction values), at intubation, and subsequently at an interval of every 1 minute for a total of five minutes. The maximum and minimum values of BP and HR during the observation period were also noted. The rate pressure product (RPP) at each measuring time point was calculated. The areas under effect-time curve (AUE) of hemodynamics were calculated by time as X-axis and changes of BP and HR during the observation as Y-axis.</p><p><b>RESULTS</b>All the three groups were similar in the demographic data and intubation time. After anesthesia induction, BP and RPP in all the three groups decreased significantly compared to baseline values (P < 0. 05), while HR had no significant change. After nasotracheal intubation, BP, HR, and RPP in all three groups were significantly higher than the postinduction values (P < 0.05). In the FOB group, BP, HR, and RPP at intubation significantly increased when compared with the baseline values (P < 0.05). In the MDLS group, HR at intubation, and maximum values of diastolic blood pressure (DBP), mean arterial pressure (MAP), HR, and RPP during the observation were significantly higher than the baseline values (P < 0.05). In the GSVL group, all hemodynamic parameters at intubation and after intubation were not significantly different from the baseline values. BP, HR, and RPP at intubation, and the incidences of HR more than 100 bpm during the observation were significantly higher in the FOB group than in the other two groups (P < 0.05). BP was not significantly different during the observation between the MDLS and GSVL groups, but HR and RPP at intubation and after intubation as well as AUE(HR) were significantly higher in the MDLS group than in the GSVL group (P < 0.05). AUE(HR) and AUE(SBP) were significantly lower in the GSVL group than in the FOB group (P < 0.05).</p><p><b>CONCLUSION</b>The hemodynamic responses to nasotracheal intubation are most severe with FOB, followed by MDLS, and then GSVL.</p>

N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance rats / 生理学报

The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in group 3, but the expressions of the NR1A mRNA and NR2A mRNA in both groups were similar, while the nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA expressions were all significantly up-regulated in group 4. As compared with group 4, the expressions of nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA were significantly inhibited in group 6. These results suggest that the expressions of nNOS and NMDA receptors in spinal cord and midbrain were significantly up-regulated in the rats with morphine analgesia tolerance. Chronic co-administration of L-NAME could effectively inhibit the morphine-induced overexpressions of nNOS and NMDA receptors, and postpone the development of morphine analgesia tolerance. Based on the results of this study, it is concluded that NO/NMDA receptor in spinal cord and midbrain is closely related to the development of morphine analgesia tolerance.