应用PET监测异丙酚与异氟醚对脑内葡萄糖代谢及可能作用的中枢部位的影响

目的：应用正电子发射计算机断层扫描技术(positron emission tomography，PET)，研究静脉麻醉剂异丙酚和吸入麻醉剂异氟醚对健康自愿者脑内葡萄糖代谢的影响，分析两种麻醉剂在中枢的可能作用部位。方法：选择健康自愿者10名，每一名自愿者按随机顺序分别作3次PET扫描，1次在清醒状态下扫描作为对照，1次在异丙酚(靶控效应室浓度3．0mg／L)麻醉状态下扫描，1次在异氟醚(1．0肺泡气最低有效浓度)麻醉状态下扫描。采用18F．FDG示踪技术测定脑内葡萄糖代谢。结果：①异丙酚麻醉后，与清醒状态比全脑的葡萄糖代谢率(CMGlu)降低34．1％(P&;lt;0．05)，在丘脑、大脑皮质、小脑和海马等区域葡萄糖代谢率(rCMGlu)明显低于清醒状态(P&;lt;0．05)，其中丘脑降幅最大达51．5％。②异氟醚麻醉后，与清醒状态比全脑的CMGlu降低37％，以丘脑和扣带回降低更为显著(P&;lt;0．05)。结论：异丙酚和异氟醚麻醉后均可使全脑和脑内各区域葡萄糖代谢显著降低，其中异丙酚对丘脑、大脑皮层和海马更为敏感，这些可能是异丙酚在中枢的作用部位；而异氟醚在脑内作用的靶区可能在丘脑、扣带回。     

应用PET评估地氟醚麻醉对人脑葡萄糖代谢率的影响

目的:应用正电子发射断层扫描技术(positronemissiontomography,PET),研究地氟醚麻醉对健康自愿者脑内葡萄糖代谢率(cerebralglu-cosemetabolismrate,CMRGlu)的影响。方法:选择10名自愿者,每名自愿者分别做2次PET扫描,采用PhilipsCPETPlus扫描仪及18F-FDG标记技术测定CMRGlu,第1次在清醒状态下扫描作为对照,第2次吸入地氟醚使自愿者刚好达到意识消失。分别划出额叶、颞叶、枕叶、顶叶、丘脑、基底核、舌回、扣带回、小脑、海马、桥脑、全脑等区域的感兴趣区并计数,所得数据以x珔±s表示。比较两组间计数的差异,并与BIS进行相关分析。结果:①自愿者清醒时全脑内CMRGlu计数为1940.5±165,意识消失时CMRGlu计数降低至1645.1±201(P<0.05),降低15.2%。②与清醒组比较,麻醉后脑内局部葡萄糖代谢率(rCMRGlu)计数均显著降低9.3%～16.2%(P<0.05),而以丘脑、枕叶和舌回葡萄糖代谢率计数降低更为显著(P<0.01),分别由3045.3±164,2867.7±107和3076.6±163降至1938.2±119,2002.8±169和2227.8±158,降低36.4%,30.2%和27.6%。③CMRGlu计数与BIS之间相关性良好(r=0.986,P=0.0006)。结论:吸入地氟醚麻醉使自愿者意识消失时全脑及脑内局部CMRGlu均可显著降低,并与BIS相关。丘脑、枕叶和舌回对吸入地氟醚麻醉更为敏感,     

应用PET评估地氟醚麻醉对人脑葡萄糖代谢率的影响

目的：应用正电子发射断层扫描技术(positron emission tomogmphy，PET)，研究地氟醚麻醉对健康自愿者脑内葡萄糖代谢率(cerebral glu-cose metabolism rate,CMRGlu)的影响。方法：选择10名自愿者，每名自愿者分别做2次PET扫描，采用Philipsc PET Plus扫描仪及18F-FDG标记技术测定CMRGlu，第1次在清醒状态下扫描作为对照，第2次吸人地氟醚使自愿者刚好达到意识消失。分别划出额叶、颞叶、枕叶、顶叶、丘脑、基底核、舌回、扣带回、小脑、海马、桥脑、全脑等区域的感兴趣区并计数，所得数据以x^-&;#177;s表示。比较两组间计数的差异，并与BIS进行相关分析。结果：①自愿者清醒时全脑内CMRGlu计数为1940．5&;#177;165，意识消失时CMRGlu计数降低至1645．1&;#177;201(P&;lt;0．05)，降低15．2％。②与清醒组比较，麻醉后脑内局部葡萄糖代谢率(rCMRGlu)计数均显著降低9．3％—16．2％(P&;lt;0．05)，而以丘脑、枕叶和舌回葡萄糖代谢率计数降低更为显著(P&;lt;0．01)，分别由3045．3&;#177;164，2867．7&;#177;107和3076．6&;#177;163降至1938．2&;#177;119，2002．8&;#177;169和2227．8&;#177;158，降低36．4％，30．2％和27．6％。③CMRGlu计数与BIS之间相关性良好(r=0．986．P=0．0006)。结论：吸人地氟醚麻醉使自愿者意识消失时全脑及脑内局部CMRGlu均可显著降低，并与BIS相关。丘脑、枕叶和舌回对吸人地氟醚麻醉更为敏感，可能是地氟醚麻醉在脑内作用的主要靶区。     

应用PET监测异丙酚与异氟醚对脑内葡萄糖代谢及可能作用的中枢部位的影响

目的:应用正电子发射计算机断层扫描技术(positronemissiontomogra-phy,PET),研究静脉麻醉剂异丙酚和吸入麻醉剂异氟醚对健康自愿者脑内葡萄糖代谢的影响,分析两种麻醉剂在中枢的可能作用部位。方法:选择健康自愿者10名,每一名自愿者按随机顺序分别作3次PET扫描,1次在清醒状态下扫描作为对照,1次在异丙酚(靶控效应室浓度3.0mg/L)麻醉状态下扫描,1次在异氟醚(1.0肺泡气最低有效浓度)麻醉状态下扫描。采用18F-FDG示踪技术测定脑内葡萄糖代谢。结果:①异丙酚麻醉后,与清醒状态比全脑的葡萄糖代谢率(CMGlu)降低34.1%(P<0.05),在丘脑、大脑皮质、小脑和海马等区域葡萄糖代谢率(rCMGlu)明显低于清醒状态(P<0.05),其中丘脑降幅最大达51.5%。②异氟醚麻醉后,与清醒状态比全脑的CMGlu降低37%,以丘脑和扣带回降低更为显著(P<0.05)。结论:异丙酚和异氟醚麻醉后均可使全脑和脑内各区域葡萄糖代谢显著降低,其中异丙酚对丘脑、大脑皮层和海马更为敏感,这些可能是异丙酚在中枢的作用部位;而异氟醚在脑内作用的靶区可能在丘脑、扣带回。     

应用单光子发射式计算机断层成像评估异氟醚对健康人全脑及局部脑血流量分布的影响

目的：观察吸入不同浓度异氟醚麻醉下健康自愿者全脑血流量和局部脑血流灌注的变化特征。方法：实验于2004-05／08在解放军第四军医大学西京医院核医学科完成。选择9名签署了知情同意书的健康自愿者，分别在清醒、吸入0．5和1．0最低肺泡有效浓度异氟醚后3种状态下采用GESPECT仪进行扫描3次，勾画出额叶、颞叶、顶叶、枕叶、丘脑、基底核、舌回、扣带回、小脑、海马、全脑及全脑等区域的感兴趣区并计数，换算成血流量和局部脑血流。在麻醉过程中维持呼气末二氧化碳分压和平均动脉压相对稳定。结果：9名自愿者全部完成测试进入结果分析。④全脑血流量：清醒时，吸入0．5或1．0最低肺泡有效浓度异氟醚后比较无差异[（482&;#177;34），（496&;#177;42），（503&;#177;31）μL／（min&;#183;g），P〉0．05]。②局部脑区局部脑血流量：额叶、颞叶、顶叶、枕叶、丘脑、基底核、舌回、扣带回、小脑、海马等区域在清醒时和吸人不同浓度异氟醚后比较均无差异。结论：在保持呼气末二氧化碳分压和平均动脉压不变时，吸入异氟醚麻醉不影响人脑内血流量的分布。     

首发抑郁症治疗后局部脑葡萄糖代谢特点及与神经心理变化的关联

目的：探讨首发抑郁症患者经盐酸氟西汀治疗前后脑葡萄糖代谢率的变化及与神经心理变化的相关性，以期对抑郁症的临床诊治提供一些生物学依据。 方法：选择2003-01／09上海市精神卫生中心14例首发抑郁症患者，在治疗前均完成临床症状、认知功能评定以及正电子发射断层扫描检查。用盐酸氟西汀（百优解）治疗（平均剂量为20mg／d）12周后，其中8例患者（汉密顿抑郁量表减分率〉50％）再次完成上述检查及评定。同时期11例华山医院体检中心健康者仅完成正电子发射断层扫描及汉密顿抑郁量表评定。①观察抑郁症组和健康对照组不同脑区的局部脑葡萄糖代谢率半定量指标，抑郁症组治疗前、后不同脑区局部脑葡萄糖代谢率半定量指标。②抑郁症组盐酸氟西汀治疗后局部脑葡萄糖代谢率变化与韦克斯勒记忆量表各因素变化进行Pearson相关分析。③分别以韦克斯勒记忆量表因素中的1→100数数、100→1数数、积累、图片及再认值的变化为因变量，以相应区域局部脑葡萄糖代谢率的变化为自变量，进行逐步多元回归分析。 结果：①抑郁症组右侧额上回、右侧扣带回的局部脑葡萄糖代谢率分别为（1．11&;#177;0．05）MBq／mL，（1．21&;#177;0．07）MBq／mL，显著低于健康对照组（P〈0．05）。②治疗有效的抑郁症组右侧额上回局部脑葡萄糖代谢率（1．17&;#177;0．08）MBq／mL显著高于治疗前（1．14&;#177;0．08）MBq／mL（P〈0．05）。③治疗后，抑郁症患者韦克斯勒记忆量表中的1→100数数值的变化与右侧海马局部脑葡萄糖代谢率的变化里正相关；100→1数数值、理解值的变化与左侧额上回局部脑葡萄糖代谢率的变化呈负相关；积累值的变化与左侧扣带回局部脑葡萄糖代谢率的变化呈正相关；图片值、触觉值的变化与左侧额中回局部脑葡萄糖代谢率的变化呈正相关；再认值的变化与左侧额下回局部脑葡萄糖代谢率的变化呈负相关；再生值的变化与右侧额下回、右侧扣带回局部脑葡萄糖代谢率的变化呈负相关；联想值的变化与左侧扣带回局部脑葡萄糖代谢率的变化呈正相关；背数值的变化与右侧枕叶局部脑葡萄糖代谢率变化呈正相关（P〈0．05或P〈0．01）；均入回归方程式，相关系数范围在0．723-0.913。 结论：盐酸氟西汀可有效提高首发抑郁症患者额上回的局部脑葡萄糖代谢率；抑郁症患者的记忆能力改善与局部脑葡萄糖代谢率改变有关。     

硬膜穿破后吸入安氟醚预防头痛的临床观察

目的：观察硬膜穿破后改用静一吸复合全麻，吸入安氟醚与异氟醚对预防术后头痛的比较。方法：ASAⅠ～Ⅱ级，择期行下腹部、会阴部手术硬膜外穿刺穿破硬膜病人26例，均改为气管插管全身麻醉。按吸入麻醉剂不同随机分成安氟醚（E）组和异氟醚（Ⅰ）组。麻醉诱导均相同：静注咪唑安定0．05mg／kg、芬太尼3Ⅱg／kg、异丙酚3mg／kg、维库溴铵0．1mg／kg，气管插管，接麻醉机。安氟醚（E）组吸入安氟醚维持全麻；异氟醚（Ⅰ）组吸入异氟醚维持全麻。术后随访3d，记录头痛情况。结果：二组病人术后头痛发生率有极显著差异（P〈0．01）。E组头痛发生率明显低于Ⅰ组。结论：硬膜穿破后改用吸入安氟醚作全麻可很好预防术后头痛。     

异氟醚对氯胺酮诱导的大鼠脑扣带回内c-fos基因表达的影响

目的：氯胺酮可以诱导c-fos在扣带回表达，并产生精神副作用，观察异氟醚对氯胺酮诱导大鼠扣带回c-fos基因表达的影响。方法：实验于2001—06在第四军医大学唐都医院动物实验室完成。SD大鼠15只，随机分为对照组．异氟醚组、氯胺酮组和异氟醚&;#177;氯胺酮Ⅰ、Ⅱ组，每组3只。异氟醚组吸人体积分数为0．02的异氟醚1h。异氟醚&;#177;氯胺酮Ⅰ组、Ⅱ组分别吸人体积分数为0．01或0．02的异氟醚5min后，腹腔注射100mg／kg氯胺酮，继续吸人异氟醚1h。对照组、氯胺酮组分别腹腔注射生理盐水、100mg／Kg氯胺酮。取脑，冰冻切片，进行Fos蛋白免疫组织化学染色。结果：实验大鼠15只均进入结果分析。①对照组、异氟醚组切片扣带回Fos蛋白免疫组织化学阳性神经元少见，两组之间无显著性差异（P〉0．05）。②氯胺酮组FOS蛋白免疫组织化学阳性神经元为126&;#177;23，显著大于对照组和异氟醚组（P〈O．01）。⑧异氟醚&;#177;氯胺酮Ⅰ组、Ⅱ组FOS蛋白免疫组织化学阳性神经元分别为54&;#177;8，11&;#177;4，显著小于氯胺酮组（P〈0．01），而且Ⅱ组FOS蛋白免疫组织化学阳性神经元数显著小于Ⅰ组（P〈0．01）。④异氟醚&;#177;氯胺酮Ⅱ组FOS蛋白免疫组织化学阳性神经元数与对照组无显著性差异（P〉0．05）。结论：异氟醚能剂量依赖的抑制氯胺酮诱导的c-fos在扣带同的表达，可以减轻或消除氯胺酮的精神副作用。     

安氟醚麻醉对人脑血流量分布的影响

目的:研究吸入不同浓度安氟醚麻醉下健康志愿者全脑血流量(cerebral blood flow,C B F)及局部脑血流量(regional cerebral blood flow,rC B F)灌注的变化特征。方法:选择9名志愿者,每位志愿者分别在清醒、吸入0.5M A C和1.0M A C安氟醚后采用SPE C T仪进行扫描,比较三者脑血流灌注的变化。结果:清醒时全脑血流量(cerebralblood flow,C B F)计数平均为135.2±27.8,吸入0.5M A C安氟醚麻醉后C B F计数平均为141.3±28.8,吸入1.0M A C安氟醚后C B F计数为139.6±27.4,三组间比较差异无显著性(P>0.05);各脑区rC B F计数也均差异无显著性(P>0.05)。结论:吸入安氟醚麻醉不影响全脑C B F及各脑区rC B F。     

应用单光子发射式计算机断层成像评估异氟醚对健康人全脑及局部脑血流量分布的影响

目的:观察吸入不同浓度异氟醚麻醉下健康自愿者全脑血流量和局部脑血流灌注的变化特征。方法:实验于2004-05/08在解放军第四军医大学西京医院核医学科完成。选择9名签署了知情同意书的健康自愿者,分别在清醒、吸入0.5和1.0最低肺泡有效浓度异氟醚后3种状态下采用GESPECT仪进行扫描3次,勾画出额叶、颞叶、顶叶、枕叶、丘脑、基底核、舌回、扣带回、小脑、海马、全脑及全脑等区域的感兴趣区并计数,换算成血流量和局部脑血流。在麻醉过程中维持呼气末二氧化碳分压和平均动脉压相对稳定。结果:9名自愿者全部完成测试进入结果分析。①全脑血流量:清醒时,吸入0.5或1.0最低肺泡有效浓度异氟醚后比较无差异[(482±34),(496±42),(503±31)μL/(min·g),P>0.05]。②局部脑区局部脑血流量:额叶、颞叶、顶叶、枕叶、丘脑、基底核、舌回、扣带回、小脑、海马等区域在清醒时和吸入不同浓度异氟醚后比较均无差异。结论:在保持呼气末二氧化碳分压和平均动脉压不变时,吸入异氟醚麻醉不影响人脑内血流量的分布。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.