Timing, method and discontinuation of hydrocortisone administration for septic shock patients

AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes.METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone.It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31 st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic(ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects.RESULTS All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h(range, 47.5-90.5) vs 108 h(range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute(range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute(range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus(83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock(r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81(P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 μg/kg per minute, with an area under the curve of 0.75(P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse(RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio(OR), 5.3; P = 0.04] and hypokalemia(OR = 10.6; P = 0.01). CONCLUSION Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.

Effects of ephedrine on expression of Nogo-A and synaptophysin in neonatal rats following hypoxic-ischemic brain damage

BACKGROUND： Central nervous system axons regenerate poorly following neonatal hypoxic-ischemic brain damage （HIBD）, partly due to inhibitors, such as Nogo-A. Very few studies have addressed the regulation of Nogo-A in neonatal rats following HIBD. However, numerous studies have shown that ephedrine accelerates neuronal remodeling and promotes recovery of neural function in neonatal rats following HIBD. OBJECTIVE： To investigate the effects of ephedrine on expression of Nogo-A and synaptophysin in brain tissues of neonatal rats following HIBD. DESIGN, TIME AND SETTING： A completely randomized, controlled study was performed at the Immunohistochemistry Laboratory of the Research Institute of Pediatrics, Children＇s Hospital of Chongqing Medical University from August 2008 to March 2009. MATERIALS： Ephedrine hydrochloride （Chifeng Pharmaceutical Group, China）, rabbit anti-Nogo-A polyclonal antibody （Abcam, UK）, and rabbit anti-synaptophysin polyclonal antibody （Lab Vision, USA） were used in this study. METHODS： A total of 96 healthy, neonatal, Sprague Dawley rats were randomly assigned to three groups （n = 32）： sham operation, HIBD, and ephedrine. The HIBD model was established by permanent occlusion of the left common carotid artery, followed by 2 hours of hypoxia （8% oxygen and 92% nitrogen）. In the sham operation group, the left common carotid artery was exposed, but was not ligated or subjected to hypoxia. Rats in the ephedrine group were intraperitoneally injected with ephedrine immediately following HIBD, with 1.5 mg/kg each time. Rats in the sham operation and HIBD groups were injected with an equal volume of saline. All neonatal rats were treated once daily for 7 days. MAIN OUTCOME MEASURES： Histopathological damage to the cortex and hippocampus was determined by hematoxylin-eosin staining. Expression of Nogo-A and synaptophysin was detected using immunohistochemical staining. RESULTS： Neuronal degeneration and edema were observed in the hypoxJc-Jschemic cortex and hippocampus by hematoxylin-eosin staining. Compared with the sham operation group, the levels of Nogo-A significantly increased in the HIBD group at various time points （P 〈 0.01）. Nogo-A expression was significantly reduced in the ephedrine group compared with the HIBD group （P 〈 0.01）. Synaptophysin expression was significantly decreased in the hypoxic-ischemJc cortex, compared with the sham operation group （P 〈 0.01）. Synaptophysin levels were significantly increased in the ephedrine group, compared with the HIBD group （P 〈 0.01）. CONCLUSION： Altered Nogo-A expression was associated with inversely altered synaptophysin expression. The use of ephedrine normalized expression levels of Nogo-A and synaptophysin following HIBD.

Effect of adrenalectomy and hydrocortisone on ventral prostate of rats

Aim: To study the effects of adrenalectomy and hydrocortisone on the ventral prostate of SD rats. Methods: Inadrenalectomised (ADX) and ADX + hydrocortisone (1, 2, or 4 mg) treated rats, the prostatic histology and thecholesterol, protein, zinc, and copper levels and the enzymic profile (acid phosphatase, alkaline phosphatase, aryl sul-phatase, lactic dehydrogenase, and leucine aminopeptidase) in the prostatic tissue were determined; the serum hormon-al profile (testosterone, FSH and LH) was also assayed. Results; Adrenalectomy caused a progressive degenerationin prostatic structure that was not reversed by hydrocortisone treatment. The serum testosterone were significantly lowerin ADX than in sham operated rats and lower in ADX + hydrocortisone than in ADX-C rats (P < 0.01). The serumFSH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham op-erated rats and higher in ADX + hydrocortisone than in ADX-C rats (P<0.05-0.01). The prostatic zinc levels weresignificantly higher in sham operated than in ADX, and higher in ADX-C than in ADX + hydrocortisone rats (P < 0.05-0.01). The prostatic copper level was significantly lower in sham operated than in ADX, and lower in ADX-C thanin the ADX + hydrocortisone rats (P <0.01). Conclusion; In rats, adrenalectomy leads to pathological and func-tional changes of the prostate. Hydrocortisone treatment at the doses employed did not reverse these changes. (Asian JAndrol 2001 Dec; 3: 289 - 300)

Crystal Structure and Thermodynamic Study of Ephedrine Hydrochloride C_(10)H_(16)NOCl(s)

The crystal structure of ephedrine hydrochloride was determined by means of X-ray crystallography. The crystal system of the compound is monoclinic, and the space group is P21. Unit cell parameters are a=0.7308（6） nm, b=0.6124（5） nm, and c= 1.2618（11） nm; β=90°, β= 102°, and γ =90°; Z=2. Low-temperature heat capacities of the title compound were measured with an improved precision automated adiabatic calorimeter over a temperature range from 77 K to 396 K. A polynomial equation of the heat capacities as a function of temperature in the temperature region was fitted by the least-squares. Based on the fitted polynomial equation, the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated and tabulated at the intervals of 5 K.

Optimal compatible doses and effects of ephedrine and naloxone on neural plasticity in cerebral ischemia/reperfusion rats

BACKGROUND： Ephedrine promotes neural plasticity in rats following cerebral ischemia/reperfusion injury. Ephedrine has been combined with naloxone in some studies, and it has been confirmed that their combination has synergistic effects on increasing neural plasticity following cerebral ischemia/reperfusion injury. OBJECTIVE： To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity and to find an optimal dose of naloxone in rats after cerebral ischemia/reperfusion injury by analyzing growth associated protein-43 （GAP-43）, synaptophysin and β-endorphin expression in the hippocampal CA3 area. DESIGN, TIME AND SETTING： This immunohistochemical, randomized, controlled, animal experiment was performed at the Chongqing Research Institute of Pediatrics, China from September 2007 to June 2008. MATERIALS： Ephedrine hydrochloride injection and naloxone hydrochloride injection were respectively purchased from Shandong Lvliang Pharmaceutical Factory, China and Sichuan Jingwei Pharmaceutical Co., Ltd., China. A total of 192 healthy adult Sprague Dawley rats were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. METHODS： At 2 hours following cerebral ischemia, the rats were intraperitoneally injected with 1.5 mg/kg/d ephedrine （ephedrine group）, with 0.1, 0.2, or 0.3 mg/kg/d naloxone （low, moderate and high doses of naloxone groups）, with 1.5 mg/kg/d ephedrine ＋ 0.1, 0.2, or 0.3 mg/kg/d naloxone （ephedrine ＋ low, moderate and high doses of naloxone groups）, and with 0.5 mL saline （model group）, respectively. MAIN OUTCOME MEASURES： GAP-43, synaptophysin and β -endorphin expression were detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery. Sensorimotor integration in rats was assessed using the beam walking test. RESULTS： GAP-43 and synaptophysin expression was greater in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group. GAP-43 and synaptophysin expression was greatest in the ephedrine ＋ high dose of naloxone group at 2 and 3 weeks alter surgery. β -endorphin expression was significantly lower in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group （P 〈 0.05）. β -endorphin expression was persistently low in the ephedrine ＋ high dose of naloxone group. At 1-3 weeks after surgery, the beam walking test score was significantly higher in the ephedrine group and ephedrine ＋ various doses of naloxone groups than in the model group （P 〈 0.05）. The score was higher in the ephedrine ＋ moderate and high doses of naloxone groups than in the ephedrine group （P 〈 0.05）. Moreover, the score was increased as the dose of naloxone increased in the ephedrine ＋ various doses of naloxone groups. CONCLUSION： Ephedrine promotes GAP-43 and synaptophysin expression, inhibits /3 -endorphin expression in the hippocampal CA3 area, and improves motor function in rats following cerebral ischemia/reperfusion injury. Naloxone does not have the above-mentioned effects. During combined treatment with ephedrine and naloxone, however, the above-described effects are enhanced with an increased dose of naloxone. The combination of ephedrine （1.5 mg/kg/d） and naloxone （0.3 mg/kg/d） can produce optimal therapeutic efficacy in treatment of cerebral ischemic injury.

Comparison the effect of ephedrine and phenylephrine in treatment of hypotension after spinal anesthesia during cesarean section

Background and Objective: The effectiveness of ephedrine and/or phenylephrine, in treatment of hypotension secondary to spinal anesthesia for cesarean section and their effects on fetal/neonatal outcome were studied. Methods and Materials: Sixty healthy parturients were randomly assigned to two groups;group E (n = 33) received boluses 5 mg/ml increments ephedrine and group P (n = 27) received a boluses of phnylephrine 100 μg/ml increments for treatment of hypotension after spinal block during cesarean section. Changes in maternal blood pressure and heart rate, and incidence of nausea-vomiting, neonatal Apgar score at 1 and 5 minutes of delivery, and umbilical arterial blood gas values were recorded. Results: There were no differences in treatment of hypotension following sympathectomy after spinal block with two drugs. Neonatal outcome was similar in two groups. There were not significant differences in umbilical arterial values in two groups. Conclusion: Ephedrine and phenylephrine are both effective vasopressores for treatment of hypotension associated to spinal block during cesarean section without adverse effects on infants/neonates.

Recombinant streptokinase vs hydrocortisone suppositories in acute hemorrhoids:A randomized controlled trial

AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(11 sites), randomized(1:1:1), open, controlled trial with parallel groups was performed. All participating patients gave their written,informed consent. After inclusion, patients with acute symptoms of hemorrhoids were centrally randomized to receive, as outpatients, by the rectal route, suppositories of rSK 200000 IU of one unit every 8 h(first 3 units)and afterwards every 12 h until 8 administrations were completed(schedule A), one unit every 8 h until 6 units were completed(schedule B), or 25 mg hydrocortisone acetate once every 8 h up to a maximum of 24 administrations. Evaluations were performed at 3, 5,and 10 d post-inclusion. The main end-point was the 5thday response(disappearance of pain and bleeding, and≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were also evaluated.RESULTS: Groups were homogeneous with regards to demographic and baseline characteristics. Fifth day complete response rates were 156/170(91.8%; 95%CI:87.3-96.2), 155/170(91.2%; 95%CI: 86.6%-95.7%),and 46/170(27.1%; 95%CI: 20.1%-34.0%) with rSK(schedule A and B) and hydrocortisone acetate suppositories, respectively. These 64.6% and 63.9%differences(95%CI: 56.7%-72.2% and 55.7%-72.0%)were highly significant(P < 0.001). This advantage was detected since the early 3rd day evaluation(68.8% and64.1% vs 7.1% for the rSK and active control groups,respectively; P < 0.001) and was maintained even at the late 10 th day assessment(97.1% and 93.5% vs67.1% for rSK and hydrocortisone acetate, respectively;P < 0.001). Time to response was 3 d(95%CI: 2.9-3.1)for both rSK groups and 10 d(95%CI: 9.3-10.7) in the hydrocortisone acetate group. This difference was highly significant(P < 0.001). All subgroup stratified analyses(with or without thrombosis and hemorrhoid classification) showed a statistically significant advantage for the rSK groups. Thrombectomy was necessary in4/251 and 14/133 patients with baseline thrombosis in the rSK and hydrocortisone acetate groups, respectively(P < 0.001). There were no adverse events attributable to the experimental treatment.CONCLUSION: rSK suppositories showed a significant advantage over a widely-used over-the-counter hydrocortisone acetate preparation for the treatment of acute hemorrhoidal illness, as well as having an adequate safety profile.

Determination of ephedrine and codeine in human urine by cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography

A sensitive method for the determination of ephedrine and codeine in human urine by capillary electrophoresis （CE） was described. In order to improve the sensitivity, two online concentration techniques including cation-selective exhaustive injection （CSEI） and sweeping micellar electrokinetic chromatography （sweeping-MEKC） were used. Under the optimum conditions, the detection limits （S/N = 3） were 0.10 μg/L for ephedrine and 0.80 μg/L for codeine. This method was successfully applied to real urine sample analysis.

A Comparative Study of Uses of Ephedrine by Different Doses on Prevention of Hemodynamic Changes Accompanied with Induction of General Anesthesia through Propofol and Fentanyl without Adverse Effects

Background: Propofol and fentanyl combination are common with general anesthesia. However, hypotension and bradycardia are common during induction of anesthetic. This study aimed to compare the response of different doses of ephedrine for attenuation of the hemodynamic changes after anesthetic induction without adverse effects. Materials and Methods: This was a randomized, double-blinded, case-controlled clinical trial. One hundred and twenty adult patients were allocated into one of the four groups: receiving IV saline, ephedrine 0.05 mg/kg, 0.1 mg/kg, or 0.2 mg/kg respectively. Induction of anesthesia was done with propofol 3 mg/kg and fentanyl 1 mg/kg. Alterations in systolic and diastolic blood pressures (SBP, DBP), mean arterial pressure (MAP), and heart rate (HR) were calculated every 1 min after induction, and 2, 3, 4 and 5 min. Then, intubation was made. Results: Baseline hemodynamic variables were comparable between groups. Patients received 0.1 mg/kg, and 0.2 mg/kg had less drop in blood pressure both systolic and diastolic, MAP, and HR with no significant rise in side effects. The numbers of patients with hypotension were significantly lower in the group receiving ephedrine 0.2 mg/kg compared to other groups (P-value 0.05). Use of IV ephedrine at a dose of 0.1 mg/kg was shown to be useful for reduction of hemodynamic changes but did not eliminate the risk of blood pressure drop. Ephedrine 0.2 mg/kg was better without causing any adverse effects. We can conclude that ephedrine 0.1 mg/kg was suitable for minimizing or decreasing changes in hemodynamic at propofol-fentanyl induction but ephedrine 0.2 mg/kg was better without causing more adverse effects.

Studies on the Stability of Corticosteroids: Degradation of Clobetasol Propionate, Desonide and Hydrocortisone in Topical Formulations by HPLC and UPLC-MS/MS

Corticosteroids are the most widely used class of anti-inflammatory medications in the pharmaceutical industry. There are several pharmaceutical dosage forms available using different corticosteroids. Topical steroids of varying potencies are available in creams, ointments, solutions and other vehicles. Chemical instability and drug degradation are the key quality concerns for these topical dosage forms. Nature of the dosage forms, excipient quality, product composition, and process optimization are some of the common factors which affect the stability of corticosteroids. This article describes drug degradation behavior of three different corticosteroids in different topical dosage forms. Drug degradation patterns of Hydrocortisone, Clobetasol propionate and Desonide formulations observed in stability studies of respective finished drug products under ICH recommended storage conditions were investigated. HPLC, UPLC-MS/MS methods were developed for the separation and characterization of impurities. The structural elucidation of the unknown impurities observed for these steroids and mechanistic consideration of potential degradation pathways has been discussed. Detailed discussion on the analytical methodologies is included as well.

Effects of Hydrocortisone, Glycerophosphate and Retinol on the Differentiation of Mesenchymal Stem Cells and Vascular Endothelial Cells to Osteoblasts

Vascular calcification, which causes occlusion and rupture of the vascular, is often observed in patients in the advanced stages of arteriosclerosis. One of the best procedures for inhibiting the accumulation of vascular calcification is to obstruct the differentiation of mesenchymal stem cells (MSCs) and/or vascular endothelial cells (VECs) in the vascular to osteoblasts. In this study, we evaluated the biochemical and genetic characteristics of the process of differentiation of MSCs and VECs to osteoblasts. C3H10T1/2 MSCs, TKD2 VECs and MC3T3-E1 preosteoblasts (POBs) were cultured in medium containing both hydrocortisone and glycerophosphate. These compounds showed strong effects promoting the differentiation of VECs as well as POBs, although the effect was weak in the MSCs. Moreover, C3H10T1/2 MSCs and TKD2 VECs were cultured in medium containing 10 mM retinol, after which the alkali phosphatase (ALP) activity of the MSCs and production of calcified nodules of TKD2 were significantly increased, whereas the marker genes for the osteoblasts were not. These results suggest that retinol does not have an effect in inducing the differentiation of VECs to osteoblasts, but rather exhibits a strong promoting effect on differentiation.

Comparative Study of Herbal Extracted Gel and 1% Hydrocortisone Gel in the Treatment of Mosquito Bite Reaction

Background: Mosquito bite reaction is a common skin disease. Topical steroids and oral antihistamines are the conventional treatment. However, the side effects from prolonged use of topical steroids are the limitation of the treatment. Recently, herbal extracts are emerging interest for an alternative anti-inflammatory dermatoses therapy. Objective: To assess the effectiveness of herbal extracted gel containing, Perilla frutescens, Portulaca oleracea, Ipomoea pescaprae, Aloe vera, Centella asiatica and Broussonetia papyrifera in comparing with 1% hydrocortisone (HC) gel. Material and Methods: An experimental study was conducted on 50 mosquito bite hypersensitive volunteers (15 - 19 years old) with double-blinded split randomized control method. After the volunteers were exposed for one bite on their arms by a non-infectious mosquito, Aedes albopictus, the drugs were applied twice daily. The diameter of lesion, pruritus analog score, erythema and melanin index were measured at 2, 6, 24 hours and 2, 3, 4 weeks. The volunteers “self-satisfaction” and side effects were recorded. Results: The mean age was 17.42 ± 1.14 years old. The diameter of lesion, pruritus analog score, erythema and melanin index were decreased on both sides at each visit with significant difference (p < 0.05). There was no significant difference between two agents of all parameters and the satisfaction of the volunteers (p > 0.05). The post-inflammatory hyperpigmentation rate of 1% HC and herbal gel was 64% and 54% respectively without significant difference (p = 0.267). Conclusion: The herbal gel was as effective as 1% HC for the treatment of acute and late reaction of mosquito bite reaction in adolescent. It may be used as the alternative treatment for mosquito bite reaction.

Effect of ephedrine hydrochloride on regulation of body fluid metabolism and AQP1 and AQP2 in a rabbit model of mechanical ventilation

Objective:Ephedrine hydrochloride(EH)is a major component from Ephedra sinica STAPF,which is used as a traditional Chinese herbal medicine.This study was designed to investigate the effect of EH on water metabolism and further explore the relevant signaling pathway of body fluid regulation in“lung governing regulation of water passage”using a rabbit model of mechanical ventilation.The molecular mechanism of the EH effect in the kidney was also investigated.Methods:Rabbits were randomly divided into a control group,model group,EH group,and dexmedetomidine hydrochloride(DH)group.Urine volume was measured by the intubation method and pathologic changes in lung and renal tissue were measured by hematoxylin and eosin staining.Nitric oxide(NO)production in lung,serum,and kidney were analyzed using chemical methods.An ELISA was used to analyze angiotensin II(Ang II),antidiuretic hormone(ADH),prostaglandin E2(PGE2),atrial natriuretic peptide(ANP),and endothelin-1(ET-1)levels in the lung,serum,and kidney.Aquaporin-1(AQP1)and aquaporin-2(AQP2)mRNA and protein expression in the kidney was determined using qRT-PCR and immunohistochemistry.Results:EH significantly inhibited the decrease in the total urine volume in the third and fourth stages,and displayed significant regulatory effects on NO,Ang II,ADH,PGE2,ANP,and ET-1 in serum,lung,and renal tissues compared with the model group.In the kidney,AQP1 and AQP2 mRNA and protein expression in the EH group were remarkably downregulated compared with the model group.Conclusion:EH exerted a regulatory effect on water metabolism by diffusing the lung and increased urine volume in the rabbit model,which was consistent with the decrease in kidney AQP1 and AQP2 expression levels that led to an increase in urine volume.EH could assist with DH to exert a protective effect on the clinical application of mechanical ventilation.

SIMULTANEOUS DETERMINATION OF EPHEDRINE AND ITS ANALOGUES IN URINE BY CAPILLARY GAS CHROMATOGRAPHY

A method is developed for the simultaneous determination of ephedrine,pseudoephedrine, norephedrine, norpseudoephedrine and methylephedrine in urine on a capillary column using nitrogen-phosphorus detector.Diphenylamine is used as the internal standard.Calibration graphs are linear down to 1.30ug/ml urine.

THE STUDIES ON THE SEPARATION AND IDENTIFICATION OF EPHEDRINES IN URINE BY GC/MSD

The separation and identification of the ephedrines(cathine,norephe-drine,ephedrine,pseudoephedrine,methylephedrine and ethylephedrine)and their derivatives obtained from TFAA,MSTFA,MSTFA+MBTFA and MSTFA+Ethyl acetate deriva- tization were carried out by GC/MSD.

Effects of ephedrine, phenylephrine and norepinephrine prevent hypotension after spinal anesthesia in cesarean section and comparison of effects on newborns

Objective: To compare the preventive effect of ephedrine, phenylephrine and norepinephrine on hypotension after lumbar anesthesia in cesarean section and their effects on newborns. Methods: 25 cesarean section women in our hospital from December 2016 to January 2018 were selected and divided into three groups according to different surgical medication, namely, ephedrine group (n=40), phenylephrine group (n=45) and norepinephrine group (n=40). Then the vital signs, neonatal blood gas analysis, neonatal Apgar score, adverse reactions of the three groups were compared. Results: The HR at T0~T3, and SBP and DBP at T0 and T1 had no difference among three groups (P>0.05). The HR, SBP and DBP at T3 ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The PCO2 and PO2 had no difference among three groups (P>0.05). The pH ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The SpO2 ranking in a descending order was phenylephrine group, ephedrine group and norepinephrine group (P<0.05). The Apgar score at birth in ephedrine group and norepinephrine group was significantly lower than that in phenylephrine group (P<0.05), while the Apgar score at post-birth 5 min and 10 min had no difference among three groups (P>0.05). The incidence of hypertension, gastrointestinal reaction, hyperhidrosis and palpitation in the phenylephrine group was significantly lower than that in the norepinephrine group (P<0.05). Conclusion: The phenylephrine and norepinephrine have no difference on the preventive effect of hypotension after spinal anesthesia in cesarean section, while safety of norepinephrine for puerpera and neonates is higher.

预防性使用阿托品对无痛膀胱镜检查术中诱发迷走神经反射的防治效果

目的:探讨预防性使用阿托品对无痛膀胱镜检查术中诱发迷走神经反射的防治效果。方法:选择2022年10月—2023年11月在青岛大学医学院松山医院行静脉复合全麻下无痛膀胱镜检查的144例患者作为研究对象,采用完全随机化分组的随机数表法将144例入选病例分为对照组、观察组,各72例。两组均采用地佐辛(0.05 mg/kg)复合1%丙泊酚(1.5~2.0 mg/kg)进行麻醉诱导,待患者睫毛反射消失时开始进行膀胱镜检查。术中丙泊酚以3~6 mg/(kg·h)维持,患者术中如发生体动,则追加丙泊酚0.5 mg/kg,直至检查结束。对照组在1%丙泊酚20 mL中加入0.9%氯化钠溶液1 mL,观察组在1%丙泊酚20 mL中加入阿托品1 mg。两组在麻醉过程中出现心率低于50次/min时,静脉注射阿托品0.5 mg,当血压降低超过20%时静脉注射麻黄碱6 mg。比较两组无痛膀胱镜检查操作时间、术后清醒时间、丙泊酚用量、术中迷走神经反射及并发症发生情况。结果:观察组无痛膀胱镜检查操作时间短于对照组,差异有统计学意义(P<0.01);两组术后清醒时间、丙泊酚用量比较,差异无统计学意义(P>0.05)。观察组术中发生迷走神经反射发生率低于对照组,差异有统计学意义(P<0.01)。两组均无严重并发症,对照组均经及时应用阿托品、麻黄碱等积极抢救治疗而痊愈。结论:无痛膀胱镜检查中预防性使用阿托品不仅有利于缩短操作时间、有利于呼吸管理,更有利于预防迷走神经反射,减少并发症,具有较高的安全性。

麻黄碱通过调控TGF-β1/NF-κB信号通路抑制小鼠的气道炎症反应

为了研究麻黄碱通过调控转化生长因子β1/核因子κB (transforming growth factor-β1/nuclear factor-κB,TGF-β1/NF-κB)信号通路对哮喘小鼠气道炎症和气道重塑的影响,将BALB/c小鼠随机分为空白对照组、哮喘模型组、麻黄碱低剂量组、麻黄碱高剂量组和地塞米松组,并利用卵清白蛋白(ovalbumin, OVA)联合氢氧化铝腹腔注射法构建小鼠哮喘模型。药物处理14 d后,通过无创性肺功能检测法测量小鼠气道反应性,采用苏木精-伊红染色法(hematoxylin-eosin staining, HE staining)观察小鼠肺组织病理情况,采用瑞氏-吉姆萨染色法分析小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)中的炎症细胞比例,利用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测小鼠血清OVA特异性免疫球蛋白E (immunoglobulin E, Ig E)的表达水平及BALF中炎症因子的表达水平,利用免疫印迹法检测小鼠肺组织TGF-β1/NF-κB通路相关蛋白质的表达水平。结果显示,麻黄碱可以降低哮喘小鼠血清中OVA特异性Ig E及BALF中白细胞介素(interleukin, IL)-4、IL-5、IL-6、IL-13、肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α)的表达水平,并显著抑制肺组织中TGF-β1/NF-κB通路相关蛋白质的表达,从而显著抑制由OVA诱导的小鼠气道高反应性,并改善哮喘小鼠的肺部炎症。

咳喘合剂质量标准研究

目的提升咳喘合剂的质量标准。方法采用薄层色谱法对咳喘合剂中麻黄、甘草、苦杏仁进行定性鉴别;依据2020年版《中国药典(四部)》进行pH、相对密度与装量检查;采用高效液相色谱法测定制剂中盐酸麻黄碱和盐酸伪麻黄碱的含量,色谱柱为Waters XBridge C_(18)柱(250 mm×4.6 mm,5μm),流动相为0.01 mol/L磷酸二氢钾溶液(用磷酸调pH至2.3)-甲醇(11∶89,V/V),流速为1.0 mL/min,柱温为35℃,检测波长为210 nm,进样量为10μL。结果麻黄、甘草、苦杏仁的薄层色谱斑点清晰,分离度良好,且阴性对照无干扰。10批样品(规格为每瓶250 mL)的pH为4.81~4.96,相对密度为1.0304~1.0477,平均装量为248~258 mL。盐酸麻黄碱及盐酸伪麻黄碱的质量浓度分别在0.523~41.800μg/mL和0.269~21.537μg/mL(r=1.0000,n=8)范围内与峰面积线性关系良好;重复性、精密度、稳定性试验结果的RSD均小于3.0%;平均加样回收率分别为92.00%和102.07%,RSD分别为2.54%和2.62%(n=6)。结论该方法操作简便、结果准确、重复性好,可用于咳喘合剂的质量控制。

近红外光谱技术无损检测克咳片中麻黄类生物碱和吗啡含量研究

麻黄类生物碱以及吗啡含量对评价克咳片质量具有重要意义,该文基于近红外光谱(NIRS)技术建立了快速、无损、高效的克咳片质量评价方法,采用NIRS和偏最小二乘回归(PLSR)法建立了麻黄类生物碱以及吗啡的定量分析模型,并采用不同预处理方法和不同变量选择方法优化了模型性能。将校正集决定系数(R_(c)^(2))、验证集决定系数(R_(p)^(2))和相对分析误差(RPD)作为模型的评价指标。结果表明,标准正态变量变换(SNV)预处理方法结合竞争自适应重加权采样(CARS)变量选择方法所建立的模型性能最优。克咳片中麻黄类生物碱及吗啡近红外光谱模型的R_(c)^(2)、R_(p)^(2)及RPD分别为0.91、0.93、4.00和0.92、0.94、4.24,说明模型性能较好。该研究基于NIRS和CARS实现了克咳片指标成分的快速、无损分析,为克咳片的质量快检提供了参考。