Syringe or mask? Loop electrosurgical excision procedure under local or general anesthesia: a randomized trial.

BACKGROUND: Loop electrosurgical excision procedure may be performed under local anesthesia or general anesthesia, and practice patterns differ worldwide. No randomized head-to-head comparison has been published to confirm or refute either practice. OBJECTIVE: This study aimed to compare loop electrosurgical excision procedure under local anesthesia vs general anesthesia regarding patient satisfaction and procedure-related outcomes such as rates of involved margins, complications, pain, and blood loss. STUDY DESIGN: Consecutive women referred to our colposcopy unit were recruited. Loop electrosurgical excision procedure was performed under local anesthesia with 4 intracervical injections of bupivacaine hydrochloride 0.5% or under general anesthesia with fentanyl, propofol, and a laryngeal mask with sevoflurane maintenance. The primary endpoint was patient satisfaction assessed on the day of surgery and 14 days thereafter using a Likert scale (score 0-100) and a questionnaire. Secondary endpoints included rates of involved margins, procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric and chi-square tests. RESULTS: Between July 2018 and February 2020, we randomized 208 women, 108 in the local anesthesia arm and 100 in the general anesthesia arm. In the intention-to-treat analysis, patient satisfaction did not differ between the study groups directly after surgery (Likert scale 100 [90-100] vs 100 [90-100]; P=.077) and 14 days thereafter (Likert scale 100 [80-100] vs 100 [90-100]; P=.079). In the per-protocol analysis, women in the local anesthesia arm had significantly smaller cone volumes (1.11 cm3 [0.70-1.83] vs 1.58 cm3 [1.08-2.69], respectively; P<.001), less intraoperative blood loss (Δhemoglobin, 0.2 g/dL [-0.1 to 0.4] vs 0.5 g/dL [0.2-0.9]; P<.001), and higher satisfaction after 14 days (100 [90-100] vs 100 [80-100]; P=.026), whereas surgeon preference favored general anesthesia (90 [79-100] vs 100 [90-100], respectively; P=.001). All other secondary outcomes did not differ between groups (resection margin status R1, 6.6% vs 2.1% [P=.26]; cone fragmentation, 12.1% vs 6.3% [P=.27]; procedure duration, 151.5 seconds [120-219.5] vs 180 seconds [117-241.5] [P=.34]; time to complete hemostasis, 60 seconds [34-97] vs 70 seconds [48.25-122.25] [P=.08]; complication rate, 3.3% vs 1.1% [P=.59]). In a multivariate analysis, parity (P=.03), type of transformation zone (P=.03), and cone volume (P=.02) and not study group assignment, age, body mass index, and degree of dysplasia independently influenced the primary endpoint. CONCLUSION: Loop electrosurgical excision procedure under local anesthesia is equally well tolerated and offers patient-reported and procedure-related benefits over general anesthesia, supporting the preferred practice in some institutions and refuting the preferred practice in others.

Comparing the insertion and ventilation of laryngeal mask airway according to the patient's head position and muscle relaxation use. A prospective clinical trial.

OBJECTIVES: To assess the insertion and ventilation of the laryngeal mask airway (LMA) classic while using different head positions with or without muscle relaxant. METHODS: This is a double-blind randomized clinical trial. Patients scheduled for ureteral calculus surgery at Shanghai General Hospital, Shanghai, China were recruited between November 2017 and November 2018. A total of 132 adults were consecutively selected. Patients were randomly divided into 4 groups according to head positioning and muscle relaxant use. An 8-cm-high pillow was used to achieve the sniffing position. The insertion time, initial peak pressure (Ppeak), mean pressure (Pmean) of the airway during intermittent positive pressure ventilation (primary endpoint) and fiberoptic score of the LMA position (secondary endpoint) were evaluated via electronic bronchoscopy through the mask bar. All adverse events were recorded. Results: Data were analyzed by ANOVA, 2-way ANOVA, Chi-squared, Cochran-Mantel-Haenszel, and Kruskal-Wallis tests. The insertion time required for the first attempt, fiberoptic score, Ppeak and Pmean did not differ among the groups. However, the incidence of adverse events in groups not using muscle relaxant was higher than in those using muscle relaxant. Conclusion: Use of a sniffing position and muscle relaxant slightly eased the insertion of the LMA but did not affect the fiberoptic score or ventilation parameters. Using a muscle relaxant, but not the sniffing position, reduced the incidence of adverse effects.

Prospective evaluation of anesthetic protocols during pediatric ophthalmic surgery.

PURPOSE: To date, no protocol of anesthesia for pediatric ophthalmic surgery is unanimously recognized. The primary anesthetic risks are associated with strabismus surgery, including oculocardiac reflex, postoperative nausea and vomiting, and postoperative pain. METHODS: This was a prospective, monocentric, observational study conducted in a tertiary pediatric ophthalmic unit. Our anesthetic protocol for strabismus surgery included postoperative nausea and vomiting prevention using dexamethasone and ondansetron. No drug-based prevention of oculocardiac reflex or local/locoregional anesthesia was employed. RESULTS: A total of 106 pediatric ophthalmic surgeries completed between November 2015 and May 2016 were analyzed. The mean patient age was 4.4 (range: 0.2-7.3, standard deviation: 2.4) years. Ambulatory rate was 90%. Oculocardiac reflex incidence was 65% during strabismus surgery (34/52), 50% during congenital cataract surgery (4/8), 33% during intramuscular injection of botulinum toxin (1/3), and 0% during other procedures. No asystole occurred. Postoperative nausea and vomiting incidence was 9.6% after strabismus surgery (5/52) and 0% following the other procedures. One child was hospitalized for one night because of persistent postoperative nausea and vomiting. Postoperative pain generally occurred early on in the recovery room and was quickly controlled. Its incidence was higher in patients who underwent strabismus surgery (27%) than in those who underwent other procedures (9%). CONCLUSION: Morbidity associated with ophthalmic pediatric surgery is low and predominantly associated with strabismus surgery. The benefit-risk ratio and cost-effectiveness of oculocardiac reflex prevention should be questioned. Our postoperative nausea and vomiting rate is low, thanks to the use of a well-managed multimodal strategy. Early postoperative pain is usually well-treated but could probably be more effectively prevented.

[Intravenous sedation with midazolam and propofol target controlled infusion on patients'perioperative anxiety under the mandibular third molar extraction].

OBJECTIVE: To evaluate whether midazolam with propofol target controlled infusion (TCI) intravenous sedation during the mandibular third molar extraction influences patients'perioperative anxiety. METHODS: The subjects were patients who planned to undergo the mandibular third molar extraction in Peking University School and Hospital of Stomatology, whose state anxiety inventory (SAI) scores were≥38 at the initial visit. They were divided into intravenous sedation group (IVS) and local anesthesia group (LA) on the basis of the planned intravenous sedation. Each group was divided into two subgroups according to the overall SAI scores at the initial visit: IVS-I, LA-I (SAI: 38-50) and IVS-II, LA-II (SAI: 51-80). The anxiety before and after the surgery was evaluated by the SAI scores at the initial visit (T1), before surgery (T2) and 7 days after surgery (T3). The anxiety during the surgery was evaluated by the heart rate, blood pressure and visual analogue scale (VAS) scores. RESULTS: There were no significant differences on SAI at T1, T2, and T3 in the two groups (P>0.05). The heart rate, blood pressure and VAS pain scores of IVS group were significantly lower than those of LA group during the surgery (P<0.001). CONCLUSION: Intravenous sedation with midazolam and propofol TCI was effective on the patients' anxiety during the third molar extraction, which successfully made the patients more comfortable and their heart rate, blood pressure and oxygen saturation more stable during the surgery. But there were no significant differences on the patients'anxiety at the initial visit (T1), before surgery (T2) and 7 days after surgery (T3) according to the SAI scores in the two groups.

Effects of preconditioning of electro-acupuncture on postoperative cognitive dysfunction in elderly: A prospective, randomized, controlled trial.

Electro-acupuncture is a burgeoning treatment using the needle inserting into the body acupoints and the low-frequency pulse current being electrified by an electric acupuncture machine. This study was designed to evaluate the effects of preconditioning of electro-acupuncture on postoperative cognitive dysfunction in elderly.Ninety patients scheduled spine surgery were randomly assigned into 2 groups using a random number table: control group (group C) and electro-acupuncture group (group EA). In group EA, electro-acupuncture was applied on Baihui, Dazhui, and Zusanli acupoints 30 minutes before anesthesia. At 0 minute before treatment of electro-acupuncture, 1 hour after skin incision and surgery completed (T1-3), blood samples were taken for detection of interleukin (IL)-6, IL-10, and S100ß by enzyme-linked immunosorbent assay. The total dose of remifentanil and propofol during surgery were recorded. Mini-Mental State Examination was applied to evaluate the cognitive function of patients at 1 day before surgery and 7th and 30th day after surgery.The results showed that compared with group C, score of MMSE increased after surgery, the serum concentration of IL-6, IL-10, and S100ß decreased at 1 hour after skin incision, and surgery completed in group EA. Moreover, the total dose of remifentanil and propofol reduced during surgery in group EA.The present study suggests that preconditioning of electro-acupuncture could improve the postoperative cognitive function, and the reduction of inflammatory reaction and brain injury may be involved in the mechanism.

A Review of Modern Control Strategies for Clinical Evaluation of Propofol Anesthesia Administration Employing Hypnosis Level Regulation.

Regulating the depth of hypnosis during surgery is one of the major objectives of an anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but it unduly increases the load of an anesthetist working in a multitasking scenario in the operation theatre. Manual and target controlled infusion systems are not appropriate to handle instabilities like blood pressure and heart rate changes arising due to interpatient and intrapatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors motivating automation in anesthesia administration. The idea of automated system for Propofol infusion excites control engineers to come up with more sophisticated systems that can handle optimum delivery of anesthetic drugs during surgery and avoid postoperative effects. A linear control technique is applied initially using three compartmental pharmacokinetic and pharmacodynamic models. Later on, sliding mode control and model predicative control achieve considerable results with nonlinear sigmoid model. Chattering and uncertainties are further improved by employing adaptive fuzzy control and H∞ control. The proposed sliding mode control scheme can easily handle the nonlinearities and achieve an optimum hypnosis level as compared to linear control schemes, hence preventing mishaps such as underdosing and overdosing of anesthesia.

Propofol alleviates liver oxidative stress via activating Nrf2 pathway.

BACKGROUND: Nuclear factor-E2-related factor 2 (Nrf2)-mediated antioxidant response is the main protective system of graft-liver against ischemia-reperfusion injury after liver transplantation. Propofol is considered to confer protective effects on different organs; thus, we explored the possibility that whether propofol could attenuate graft-liver injury in a rat autologous orthotopic liver transplantation (AOLT) model and mechanisms were associated with activation of Nrf2 pathway. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham-operated group, saline-treated AOLT group, low-dose propofol intervention group, and high-dose propofol intervention group. Liver injury was determined, and concentration of hydroxyl free radical (•OH), superoxide anion (O2(•-)), and malondialdehyde in the liver tissue were detected. The expression of Keap1, Nrf2, HO-1, and NQO1 were explored by Western blotting, and also the change of Nrf2 and keap1 was assessed by immunofluorescence. RESULTS: Compared with sham group, pathologic damage of graft-livers was in a time-dependent manner, accompanied with the increased level of oxidative stress in the AOLT group, and nuclear Nrf2 expression and its downstream antioxidant enzyme, HO-1 and NQO1, were also increased in this group. However, in propofol pretreatment groups especially in the high-dose group, the pathologic score was significantly decreased, accompanied with a lower level of •OH, O2(•-), and malondialdehyde than that of the AOLT group. The change of oxidative stress might be related to the Nrf2 pathway, evidenced as the elevation of protein expression level of NQO1, HO-1, and nuclear Nrf2. CONCLUSIONS: Protective effects of propofol against liver transplantation-induced graft-liver injury may be related with Keap1-Nrf2 signal pathway activation.

Intubation without muscle relaxation for suspension laryngoscopy: a randomized, controlled study.

OBJECTIVE AND AIM: The objective of the following study is to examine the effectiveness and safety of suspension laryngoscopy under intubation with propofol and remifentanil alone for vocal fold nodule (VFN) excision. MATERIALS AND METHODS: A total of 40 patients were equally and randomly assigned to elective VFN excision using suspension laryngoscopy under intubation with propofol and remifentanil alone (Group A) or with supplementary cisatracurium (Group B). RESULTS: Intubation time was significantly longer in Group A than in Group B (300.0 ± 30.0 s vs. 265.2 ± 38.7 s, P = 0.003). The two groups showed similar Cormack-Lehane classifications, intubation conditions and ease of suspension laryngoscopy. Both groups showed favorable cardiopulmonary safety profiles. Post-anesthesia recovery was significantly more rapid in Group A than in Group B, in terms of times to spontaneous breathing return (7.2 ± 1.4 min vs. 10.9 ± 1.6 min, P < 0.001), consciousness return (7.4 ± 1.5 min vs. 12.3 ± 1.8 min, P < 0.001), removal of tracheal intubation (8.1 ± 1.5 min vs. 13.2 ± 1.7 min, P < 0.001) and operating room discharge (12.7 ± 1.4 min vs. 22.1 ± 1.3 min, P < 0.001). CONCLUSION: Use of propofol and remifentanil alone provides favorable intubation and anesthesia conditions for suspension laryngoscopic VFN excision and accelerates post-anesthesia recovery.

The effect of preoperative consumption of potatoes on succinylcholine-induced block and recovery from anesthesia.

Potatoes contain solanaceous glycoalkaloids (SGAs), which inhibit both butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The present study investigated the effect of preoperative consumption of potatoes on succinylcholine-induced block and recovery from anesthesia. ASA I-II, adult patients, scheduled for elective surgery, were included in a randomized, blind and controlled study. Patients were randomly divided into two groups. Patients in Group P (n = 21) ate a standard portion of potatoes in their last meal prior to pre-operative fasting, while patients in Group C (n = 23) ate food not containing SGAs. Patients were premedicated with midazolam. Anesthesia was induced with thiopental and fentanyl, and maintained with sevoflurane in 50 % O2/air and fentanyl, as needed. Succinylcholine 1 mg kg(-1) was administered to facilitate endotracheal intubation. Duration of succinylcholine blockade, awakening and recovery times from anesthesia were measured. Serum BuChE levels were also measured at baseline and 4 time-points within 24 h post-consumption. Duration of succinylcholine-induced neuromuscular block, awakening and recovery time from anesthesia was significantly longer in Group P than in Group C (p < 0.05). Serum BuChE levels decreased at 6 h after consumption start in Group P. In addition, in both groups, BuChE levels markedly decreased after succinylcholine blockade, increased thereafter, but did not return to baseline within 24 h of consumption start. None of these differences observed in BuChE levels was statistically significant. This study suggests that potatoes eaten before anesthesia can prolong the duration of succinylcholine-induced neuromuscular block and delay recovery from anesthesia.

Electromyographic response of facial nerve stimulation under different levels of neuromuscular blockade during middle-ear surgery.

OBJECTIVE: To investigate facial nerve monitoring in patients receiving the partial nondepolarizing neuromuscular blocking agents (NMBAs), remifentanil and propofol. METHODS: Patients with normal facial function and advanced middle-ear disease were enrolled. For total intravenous anaesthesia (TIVA), propofol and remifentanil were infused as induction/maintenance anaesthesia. Stimulation thresholds and amplitudes were recorded at each train-of-four (TOF) nerve stimulation level. Time differences between start of TOF and electromyographic (EMG) amplitude decreases (Ti), and between complete recovery of TOF and EMG amplitudes (Tr), were calculated. RESULTS: Fifteen patients were enrolled. Mean ± SD Ti was 3.4 ± 1.28 min; Tr was 18.7 ± 4.41 min. Amplitude of stimulation was apparent mostly at TOF level 1. In most cases, no or a weak response (<100 µV) was observed at TOF 0. Mean ± SD threshold of electrical stimulation was 0.31 ± 0.10 mA at TOF 1. At TOF > 2, all cases showed EMG response on electrical stimulation. CONCLUSIONS: Induction of TIVA using propofol and remifentanil provided reliable conditions for delicate microsurgery. Minimal NMBA use, considered as producing TOF levels >1, was sufficient for facial nerve monitoring in neuro-otological surgery.

HCN1 channels as targets for anesthetic and nonanesthetic propofol analogs in the amelioration of mechanical and thermal hyperalgesia in a mouse model of neuropathic pain.

Chronic pain after peripheral nerve injury is associated with afferent hyperexcitability and upregulation of hyperpolarization-activated, cyclic nucleotide-regulated (HCN)-mediated IH pacemaker currents in sensory neurons. HCN channels thus constitute an attractive target for treating chronic pain. HCN channels are ubiquitously expressed; analgesics targeting HCN1-rich cells in the peripheral nervous system must spare the cardiac pacemaker current (carried mostly by HCN2 and HCN4) and the central nervous system (where all four isoforms are expressed). The alkylphenol general anesthetic propofol (2,6-di-iso-propylphenol) selectively inhibits HCN1 channels versus HCN2-HCN4 and exhibits a modest pharmacokinetic preference for the periphery. Consequently, we hypothesized that propofol, and congeners, should be antihyperalgesic. Alkyl-substituted propofol analogs have different rank-order potencies with respect to HCN1 inhibition, GABA(A) receptor (GABA(A)-R) potentiation, and general anesthesia. Thus, 2,6- and 2,4-di-tertbutylphenol (2,6- and 2,4-DTBP, respectively) are more potent HCN1 antagonists than propofol, whereas 2,6- and 2,4-di-sec-butylphenol (2,6- and 2,4-DSBP, respectively) are less potent. In contrast, DSBPs, but not DTBPs, enhance GABA(A)-R function and are general anesthetics. 2,6-DTBP retained propofol's selectivity for HCN1 over HCN2-HCN4. In a peripheral nerve ligation model of neuropathic pain, 2,6-DTBP and subhypnotic propofol are antihyperalgesic. The findings are consistent with these alkylphenols exerting analgesia via non-GABA(A)-R targets and suggest that antagonism of central HCN1 channels may be of limited importance to general anesthesia. Alkylphenols are hydrophobic, and thus potential modifiers of lipid bilayers, but their effects on HCN channels are due to direct drug-channel interactions because they have little bilayer-modifying effect at therapeutic concentrations. The alkylphenol antihyperalgesic target may be HCN1 channels in the damaged peripheral nervous system.

Propofol prevents lung injury following intestinal ischemia-reperfusion.

BACKGROUND: The antioxidant properties of propofol have been shown to improve ischemia/reperfusion injury. We investigated whether anesthesia with propofol can ameliorate remote lung injury induced by intestinal ischemia-reperfusion (IIR). MATERIALS AND METHODS: Thirty male Wistar rats were randomly allocated in three groups (n = 10 each): animals in group Sham were anesthetized with ketamine and xylazine and then laparotomy and sham IIR followed. Animals in group IIR received ketamine and xylazine and were then subjected to clamping of the superior mesenteric artery for 45 min and reperfusion for 4 h. Group IIR+P received anesthesia with propofol and then IIR was induced, as in group IIR. Blood samples for blood gases and malondialdehyde measurements were drawn at the end of reperfusion. Bronchoalveolar lavage fluid (BALF) was obtained to measure cell counts, total protein, and phospholipids levels. RESULTS: Induction of IIR resulted in deteriorated oxygenation, acidemia, and inflammatory cells sequestration, along with increased BALF protein content and increased proportions of small surfactant aggregates. Anesthesia with propofol alleviated intestinal injury and efficiently prevented lipid oxidation. In group IIR+P inflammatory cell infiltration and pulmonary histologic changes were significantly limited. The increase in BALF total protein and the changes in surfactant aggregates were prevented, leading to normal systemic oxygenation. CONCLUSION: Using propofol to induce and maintain anesthesia efficiently prevented IIR-induced lung injury. Systemic antioxidant protection, improvement of intestinal injury, inhibition of the inflammatory response, and preservation of the alveolar-capillary permeability seem to be crucial mediating mechanisms for this simple and clinically relevant intervention.

Remifentanil patient-controlled analgesia for labour: a complete audit cycle.

Remifentanil patient-controlled analgesia (PCA) was introduced to a small maternity unit where an extensive epidural service was difficult to provide. This was a new service and the New Zealand College of Midwives had serious doubts about the efficacy and safety of remifentanil, so auditing its use was important. In a two-stage audit, clinical notes of 244 consecutive remifentanil users were studied between January 2008 and November 2009. We developed a questionnaire to assess the parturients' satisfaction with remifentanil PCA and designed a proforma to evaluate it against four standards of best practice. During the two audit periods, timely commencement of PCA was achieved in 65% and 82% of cases, respectively. A 70% compliance rate with monitoring standards fell to 10% after the withdrawal of supervision by an acute pain team, but improved to 91% following implementation of regular midwifery training sessions and a redesigned partogram and prescription flowchart. Ninety-four percent of women rated remifentanil PCA as excellent, very good or good. Maternal side-effects were nausea, pruritus and drowsiness. A comparison of Apgar scores of consecutive neonates born by normal vaginal delivery to women receiving no analgesia, with those born to women using remifentanil PCA, demonstrated no difference. As a result of our audit, remifentanil PCA is now viewed by our midwives as an effective and safe method when accompanied by 1:1 care and appropriate monitoring. With our input other maternity units have introduced it, especially where epidural service provision is limited, and for patients in whom epidural analgesia is contraindicated.

Rapid hypnosis as an anaesthesia adjunct for evacuation of postpartum vulval haematoma.

Hypnosis can be a useful therapeutic adjunct to pharmacological analgesia or anaesthesia in obstetrics. However, it is rarely considered a primary anaesthetic technique and is seldom employed in the acute surgical setting. Few obstetricians and anaesthetists currently utilise this technique in their clinical practice. We present a case report of a 34-year-old woman who successfully underwent evacuation of a large vulval haematoma using the simple hypnosis technique of 'believed-in imagination' as the principal anaesthetic technique with only minimal adjunctive pharmacological analgesia.

Median effective effect-site concentration of intravenous anesthetics for loss of consciousness in neoadjuvant chemotherapy patients.

BACKGROUND: In recent years, increasing numbers of patients are accepting neoadjuvant chemotherapy before their operation in order to get a better prognosis. But chemotherapy has many side-effects. We have observed that patients who accepted neoadjuvant chemotherapy are more sensitive to anesthetics. The aim of this study was to determine the median effective dose (EC(50)) of intravenous anesthetics for neoadjuvant chemotherapy patients to lose consciousness during target-controlled infusion. METHODS: Two hundred and forty breast cancer patients undergoing elective operations were assigned to six groups according to treatment received before their operation and the use of intravenous anesthetics during anesthesia; non-adjuvant chemotherapy + propofol group (group NP, n = 40), Taxol + propofol group (group TP, n = 40), adriamycin + cyclophosphamide + 5-Fu + propofol group (group CP, n = 40), non-adjuvant chemotherapy + etomidate group (group NE, n = 40), taxol + etomidate group (group TE, n = 40), adriamycin + cyclophosphamide + 5-Fu + etomidate group (group CE, n = 40). We set the beginning effect-site concentration (Ce) of propofol as 3.0 µg/ml and etomidate as 0.2 µg/ml. The concentration was increased by steps until the patient was asleep, (OAAS class I-II), then gave fentanyl 3 µg/kg and rocuronium 0.6 mg/kg and intubated three minutes later. The patients' age, height, and weight were recorded. BIS was recorded before induction, at the initial effect-site concentration and at loss of consciousness. The effect-site concentration was recorded when patient lost consciousness. RESULTS: There were no significant differences between groups in general conditions before treatment; such as BIS of consciousness, age, sex and body mass index. The EC(50) of propofol in the NP, TP and CP groups was 4.11 µg/ml (95%CI: 3.96 - 4.26), 2.94 µg/ml (95%CI: 3.36 - 3.47) and 2.91 µg/ml (95%CI: 3.35 - 3.86), respectively. The EC50 of etomidate in the NE, TE and CE groups was 0.61 µg/ml (95%CI: 0.55 - 0.67), 0.38 µg/ml (95%CI: 0.33 - 0.44), and 0.35 µg/ml (95%CI: 0.34 - 0.36), respectively. There was no significant difference of BIS level before induction or in BIS50 level in any group when patients lost consciousness. CONCLUSIONS: The EC(50) of intravenous anesthetics to cause loss of consciousness in neoadjuvant chemotherapy groups is lower than in the control group. There was no significant difference of BIS level at which patients lost consciousness.

Propofol inhibits lipopolysaccharide-induced lung epithelial cell injury by reducing hypoxia-inducible factor-1alpha expression.

BACKGROUND: Lipopolysaccharide (LPS) may activate hypoxia-inducible factor (HIF)-1α, which up-regulates cytokine expression and the lethality of LPS-induced shock. We investigated the effect of propofol on HIF-1α expression and acute lung injury in LPS-treated mice. METHODS: A series of both positive and negative control experiments were performed. We injected BALB/C mice with propofol or vehicle i.p. immediately and 12 h after an LPS challenge. After 24 h, we examined the lung wet/dry weight ratio, neutrophil infiltration, and HIF-1α mRNA expression and inflammatory cytokines in the lung tissue. Survival was determined for 48 h after LPS injection. In vitro, we determined the responses of A549 cells, with and without HIF-1α silenced, to treatment with LPS alone and LPS plus propofol. RESULTS: Propofol prolonged survival and attenuated acute lung injury and decreased the expression of HIF-1α, interleukin (IL)-6, keratinocyte-derived chemokine, and tumour necrosis factor-alpha (TNF-α) in the lungs of endotoxaemic mice. In HIF-1α knockdown-A549 cells, LPS-induced TNF-α, IL-6, and the pro-apoptotic gene, BNIP3 expression and apoptosis were reduced. Propofol, but not an inhibitor of nuclear factor κB, reduced HIF-1α expression in LPS-stimulated A549 cells. Propofol also down-regulated, in A549 cells, the expression of IL-6, IL-8, and TNF-α, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), and apoptosis. CONCLUSIONS: Propofol reduces apoptosis in LPS-stimulated lung epithelial cells by decreasing HIF-1α, BNIP3, and cytokine production. Using propofol to inhibit HIF-1α expression may protect against the acute lung injury caused by LPS-induced sepsis.

Synergy of isoflurane preconditioning and propofol postconditioning reduces myocardial reperfusion injury in patients.

Either isoflurane preconditioning or high-dose propofol treatment has been shown to attenuate myocardial IRI (ischaemia/reperfusion injury) in patients undergoing CABG (coronary artery bypass graft) surgery. It is unknown whether isoflurane and propofol may synergistically attenuate myocardial injury in patients. The present study investigated the efficacy of IsoPC (isoflurane preconditioning), propofol treatment (postconditioning) and their synergy in attenuating postischaemic myocardial injury in patients undergoing CABG surgery using CPB (cardiopulmonary bypass). Patients (n = 120) selected for CABG surgery were randomly assigned to one of four groups (n = 30 each). After induction, anaesthesia was maintained either with fentanyl and midazolam (control; group C); with propofol at 100 µg x kg(-1) of body weight x min(-1) before and during CPB followed by propofol at 60 µg x kg(-1) of body weight x min(-1) for 15 min after aortic declamping (group P); with isoflurane 1-1.5% end tidal throughout the surgery (group I) or with isoflurane 1-1.5% end tidal before CPB and switching to propofol at 100 µg x kg(-1) of body weight x min(-1) during CPB followed by propofol at 60 µg x kg(-1) of body weight x min(-1) for 15 min after aortic declamping (group IP, i.e. IsoPC plus propofol postconditioning). A joint isoflurane and propofol anaesthesia regimen synergistically reduced plasma levels of cTnI (cardiac troponin I) and CK-MB (creatine kinase MB) and f-FABP (heart-type fatty acid-binding protein) (all P < 0.05 compared with control, group P or group I) and facilitated postoperative myocardial functional recovery. During reperfusion, myocardial tissue eNOS (endothelial NO synthase) protein expression in group IP was significantly higher, whereas nitrotyrosine protein expression was lower than those in the control group. In conclusion, a joint isoflurane preconditioning and propofol anaesthesia regimen synergistically attenuated myocardial reperfusion injury in patients.

Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the activation of different descending pain inhibitory mechanisms.

UNLABELLED: We evaluated the effectiveness of intrathecal antagonists of α1- (WB4101) and α2- (idazoxan) adrenoceptors and serotonergic (methysergide), opioid (naloxone), muscarinic (atropine), GABA(A) (bicuculline) and GABA(B) (phaclofen) receptors in blocking 2- or 100-Hz electroacupuncture (EA)-induced analgesia (EAIA) in the rat tail-flick test. EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints in lightly anesthetized rats. EA increased tail-flick latency, where the effect of 2-Hz EA lasted longer than that produced by 100-Hz EA. The 2-Hz EAIA was inhibited by naloxone or atropine, was less intense and shorter after WB4101 or idazoxan, and was shorter after methysergide, bicuculline, or phaclofen. The 100-Hz EAIA was less intense and shorter after naloxone and atropine, less intense and longer after phaclofen, shorter after methysergide or bicuculline, and remained unchanged after WB4101 or idazoxan. We postulate that the intensity of the effect of 2-Hz EA depends on noradrenergic descending mechanisms and involves spinal opioid and muscarinic mechanisms, whereas the duration of the effect depends on both noradrenergic and serotonergic descending mechanisms, and involves spinal GABAergic modulation. In contrast, the intensity of 100-Hz EAIA involves spinal muscarinic, opioid, and GABA(B) mechanisms, while the duration of the effects depends on spinal serotonergic, muscarinic, opioid, and GABA(A) mechanisms. PERSPECTIVE: The results of this study indicate that 2- and 100-Hz EA induce analgesia in the rat tail-flick test activating different descending mechanisms at the spinal cord level that control the intensity and duration of the effect. The adequate pharmacological manipulation of such mechanisms may improve EA effectiveness for pain management.

Comparisons of two different doses of fentanyl for procedural analgesia during epidural catheter placement: a double-blind prospective, randomized, placebo-controlled study.

The purpose of this study was to investigate the effect of fentanyl on analgesic properties and respiratory responses during an epidural procedure. Sixty patients premedicated with oral brotizolam 0.25 mg were allocated to receive procedural analgesia with saline or 25 or 50 µg of fentanyl. Five minutes after administration, an epidural procedure was started. Pain assessments were made immediately after the epidural catheter placement using a visual analog scale. The lowest SpO2 levels during the procedure were recorded to evaluate respiratory depression, and cardiovascular complications were also recorded. The pain scores were significantly lower in the 25 and 50 µg fentanyl groups than in the placebo group (P < 0.01). There was no difference in pain assessment between the 25 and 50 µg fentanyl groups. The lowest SpO2 value of the 50 µg fentanyl group was significantly lower than those of the other groups (P < 0.001). Seven of 20 cases in the 50 µg fentanyl group needed oxygen administration because of a decreased SpO2 value (<94%). No cardiovascular complications were observed in any group during the entire study period. Thus, intravenous fentanyl at a dose of 25 µg provides effective procedural analgesia without the risk of hypoxemia during an epidural procedure in a patient with preanesthetic medication.