表面麻醉下早产儿视网膜激光光凝术治疗的应激反应研究
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摘要
研究背景：
早产儿是指胎龄在37足周以前出生的活产婴儿；新生儿是指出生后至28天的婴儿,此时期的婴儿刚刚从母亲子宫内来到外界生活,还处在适应期。由于这段时期新生儿各系统脏器功能发育尚未成熟,免疫功能低下,体温调节功能较差,因而与成人相比,生命力脆弱。而新生早产儿,由于各器官发育程度远远落后,生存率大大下降。此时期若机体受到各种伤害性刺激,如创伤、失血、缺氧、疼痛、冷热、恐惧、剧烈运动、急性感染和手术麻醉等,引起机体各种功能和代谢过程的变化,可在全身范围内引起一系列广泛的反应,包括神经系统、内分泌系统、免疫系统的反应及发生应激性细胞凋亡等,而引起的应激反应,甚至可以威胁到新生早产儿的生命安全。作为临床医护工作者,在治疗和护理患儿原发病的同时,应当极力避免这种情况的发生。
多年来,儿童在手术时产生的应激反应一直备受关注。大型儿童外科手术会在患儿生命体征稳定的前提下进行全身麻醉后进行,这使得患儿所受到的应激反应及其所面临的危险程度大大减小。但是,微小程度刺激所引起的应激反应没有得到足够重视。对于新生早产儿而言,由于全身基础情况差,即使受到微小刺激,也可能引起新生早产儿严重的应激反应。
早产儿视网膜病变(retinopathy of prematurity, ROP)是一种较为常见的威胁新生儿视力的眼科疾病,可能严重影响其未来生活质量。及早进行ROP筛查和激光治疗,是避免ROP致盲的关键。由于ROP激光光凝术的对象均是各器官发育尚未成熟的早产儿,国内外学者认识到,无论是采用全身麻醉还是表面麻醉,两种方式均有不同程度的风险存在。实践中,本医院对多数ROP患儿采用在表面麻醉下治疗,虽然多数患儿都完成整个治疗过程,但是,通过观察可以发现,仍然有患儿在治疗中或治疗后全身状况出现异常。那么,这些被诊断为ROP的患儿出现这些问题的根源何在?在表面麻醉下进行ROP激光光凝术的早产儿在治疗中是否会产生应激反应,为何会产生应激反应,会产生怎样的应激反应?临床上,应当如何通过更加具有针对性的干预措施,预防与减轻这种应激反应,从而保证患儿在接受治疗过程中的生命安全,目前相关的研究报道在国内外不多。
近年来国内外研究表明,在胎儿时期感受疼痛的神经传导通路就已发育完善,因此,即使是早产儿,在出生后就已具备感受疼痛的能力。而且,早产儿对疼痛的感受较年长儿更为敏感。Anand等提出,疼痛是新生儿的潜在特质,是个体发育早期的组织损伤信号系统,并且认为新生儿期疼痛的生理和行为反应可替代主观自述而作为有效的评估疼痛的指标。虽然患儿由于年龄小等原因无法对疼痛程度大小进行描述,但已有相关报道,采用国际常用的视觉模拟评分法(visual analogue scale, VAS)对疼痛程度进行评分。
Mahta等将76名早产儿分为两组,使用不同的ROP筛查方法,对早产儿的疼痛情况进行研究,结果表明,无论使用何种ROP筛查方法,开睑器对患儿造成的疼痛是最大的。Dhaliwal等对40名早产儿在ROP筛查时,使用PIPP量表进行疼痛评分,结果显示,使用开睑器时,无论是间接的眼底镜检查还是直接的视网膜照相机检查,婴儿都有相似的疼痛分值。他们的研究共同表明,眼科检查带来的大多数疼痛源于开睑器的使用,而不是检查方式本身的问题。
Mukherjee等用心肺的指标去评估直接的视网膜照相机检查和间接眼底镜检查对86名早产儿造成的刺激,研究记录检查前、检查过程中和检查后1小时的心率、血氧饱和度、呼吸频率和平均血压,统计后发现心率和呼吸频率在间接眼底镜检查中较高。
视网膜激光光凝术治疗看似只是一个“微小刺激”,但成人糖尿病视网膜病变患者在接受全视网膜光凝过程中是有疼痛感的,眼底病变程度越重,患者在激光光凝时的疼痛感也相应更重,增殖期的疼痛感觉重于非增殖期。而有关视网膜激光光凝术治疗是否会导致早产儿产生应激反应的研究尚未见报道。这使得临床工作者在工作中缺乏对该治疗方法安全隐患的预期,也缺乏对患儿进行早期干预的科学依据。
目前,外科、大手术护理均有相应的护理常规,而表面麻醉下行视网膜激光光凝术治疗的护理常规均为各医院自行制定,尚无统一、规范的护理常规；而且,在临床工作中,医护工作者容易忽视对表面麻醉下处于清醒状态患儿的监测,使患儿的异常状况未能被医护人员及时发现,而导致不良医疗事件的发生。
因此,本研究在国内率先以表面麻醉下视网膜激光光凝术治疗为“微小刺激”模型,将实验室检测与临床监测相结合,从科学的角度探讨表面麻醉下视网膜激光光凝术治疗是否会使早产儿产生应激反应,了解该治疗方法存在的安全隐患,为临床医护工作者采取针对性的干预措施提供科学依据,避免严重医疗事故的发生,同时也为临床医护工作者今后进行类似“微小刺激”的研究提供参考。
研究目的：
1.本研究以实验室检测为重点,了解表面麻醉下接受视网膜激光光凝术治疗的早产儿在治疗前后不同时间点血液中应激相关生化指标的变化,从科学的角度探讨表面麻醉下接受视网膜激光光凝术治疗的早产儿在治疗中是否会产生应激反应。
2.结合临床工作中对表面麻醉下视网膜激光光凝术治疗时,早产儿生理指标监测,以更全面的角度探讨在治疗中应激反应存在与否；分析导致表面麻醉下视网膜激光光凝术治疗应激反应产生原因,以及表面麻醉下视网膜激光光凝术治疗存在安全隐患。
3.本研究为临床医护工作者共同制定表面麻醉下视网膜激光光凝术治疗的干预措施与护理常规提供科学依据,将避免或减少激光光凝术并发症的发生,既可以使ROP患儿能够获得安全、及时的治疗,从而减少新增人口的致盲率；又使患儿的生活质量得到提高,减轻家庭、社会的负担。
4.本研究对医护人员如何为表面麻醉下视网膜激光光凝术治疗的早产儿监测及治疗提供循证依据,规范护理操作流程。
5.通过研究视网膜激光光凝术治疗这种“微小刺激”对早产儿造成的影响,为临床其他类似的“微小刺激”操作提供参照,减少医疗意外事故的发生,在治疗早产儿原发病的同时,使患儿的生命安全得到保障。
研究方法：
1.对表面麻醉下进行视网膜激光光凝术的早产儿,分别于治疗前安静状态、治疗结束时、治疗后1h、治疗后24h抽取其静脉血2ml,采用实验室检查的方法,检测血液中多巴胺、去甲肾上腺素、肾上腺素、皮质醇、促肾上腺皮质激素(adreno-cortico-tropic-hormone, ACTH)、血糖、C反应蛋白(C-reactive protein, CRP)7个与应激相关生化指标的浓度变化。
2.使用心电监护仪对表面麻醉下接受视网膜激光光凝术的早产儿进行监测,记录视网膜激光光凝术治疗前安静状态、治疗结束时、治疗后1h、治疗后24h其心率(heart rate, HR)、血氧饱和度(oxygen saturation of blood, SpO2)、呼吸频率(respiratory rate, RR)、平均动脉压(mean artery pressure, MAP)的变化；记录并统计在激光光凝术治疗过程中早产儿生理指标(SPO2、HR、 MAP)的变化幅度。
3.数据录入及统计学方法：研究数据收集后直接交给数据统计人员,录入后进行双人核对。采用SPSS13.0统计软件进行数据处理,各检测指标以均数±标准差(x±s)表示,采用重复测量设计的方差分析,组间多重比较采用LSD法,以α=0.05(双侧)为检验水准,P<0.05时差异有统计学意义。
结果：
1.30例表面麻醉下视网膜激光光凝术治疗前后患儿血液中应激相关生化指标变化：
1.1患儿不同时间点多巴胺水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h患儿多巴胺的水平高于治疗前安静状态,差异有统计学意义(P<0.05)；
1.2患儿不同时间点去甲肾上腺素水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h患儿去甲肾上腺素的水平高于治疗前安静状态,差异有统计学意义(P<0.05)；
1.3患儿不同时间点肾上腺素水平组间总的比较差异有统计学意义(P<0.05),治疗结束时肾上腺素水平高于治疗前安静状态,差异有统计学意义(P<0.05)：
1.4患儿不同时间点皮质醇水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h患儿皮质醇的水平高于治疗前安静状态,差异有统计学意义(P<0.05)；
1.5患儿不同时间点ACTH水平组间总的比较差异有统计学意义(P<0.001),治疗结束时患儿ACTH的水平高于治疗前安静状态,差异有统计学意义(P<0.001)；
1.6患儿不同时间点血糖水平组间总的比较差异有统计学意义(P<0.001),治疗结束时患儿血糖的水平高于治疗前安静状态,差异有统计学意义(P<0.001)；
1.7患儿不同时间点CRP水平组间总的比较差异无统计学意义(P>0.05)。
2.表面麻醉下视网膜激光光凝术治疗前后患儿生理指标的变化：
2.1患儿不同时间点HR水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h、治疗后24h患儿HR的变化与治疗前安静状态相比,差异有统计学意义(P<0.05)：
2.2患儿不同时间点MAP水平组间总的比较差异有统计学意义(P<0.001),治疗结束时患儿MAP的水平高于治疗前安静状态,差异具有统计学意义(P<0.001))；
2.3患儿不同时间点RR水平组间总的比较差异有统计学意义(P<0.001)；治疗结束时、治疗后1h、治疗后24h患儿RR的水平均高于治疗前安静状态,差异有统计学意义(P<0.05)；
2.4患儿不同时间点Sp02水平组间总的比较差异有统计学意义(P<0.001)；治疗后1h、治疗后24h SpO2高于治疗前安静状态下的水平,差异有统计学意义(P<0.05)
3.视网膜激光光凝术治疗过程中患儿生理指标的变化
3.1Sp02的变化：2例(6.7%)患儿Sp02降至80%以下,1例(3.3%)患儿在80%-90%水平,27例(90%)患儿Sp02均维持在90%以上。
3.2HR与MAP的变化：2例(6.7%)患儿的HR与MAP的下降幅度≥治疗前水平20%,13例(43.3%)患儿的升降幅度<治疗前水平20%,15例(50%)患儿的HR与MAP的升高幅度≥治疗前水平的20%。
结论及对临床工作者的提示：
1.在表面麻醉下进行ROP激光光凝术治疗的早产儿,治疗过程中会产生应激反应。
2.通过实验室检测早产儿血液中应激相关生化指标的变化,可以证明其在激光光凝术治疗过程中存在应激反应。
3.通过临床监测早产儿生理指标的改变能反映视网膜激光光凝术治疗过程中应激反应的存在。
4.由于实验室检测在时效方面的局限性,临床医护工作者应当重视对表面麻醉下视网膜激光光凝术早产儿的临床监测并及时采取应对措施。
5.应激源所引起的生理指标变化为临床医护人员的监测及护理提供依据。虽然表面麻醉下的早产儿一直处于清醒状态,临床医护工作者绝对不能忽视视网膜激光光凝术治疗开始至治疗后24h这段时间内对早产儿的评估与监测,尤其应当注意HR与RR的变化,护士应加强巡视和评估,尽量避免早产儿再受到外界过多的刺激。
6.视网膜激光光凝术治疗中早产儿的应激反应是由多种应激源共同作用所导致的。
7.在临床工作中,应重视类似于视网膜激光光凝术这种“微小刺激”对早产儿造成的影响。
创新点：
1.从对血液中应激因子的实验室检测以及对其生理指标的监测结果两个方面的研究,科学论证了在表面麻醉下接受早产儿视网膜激光光凝术治疗时患儿会产生应激反应。
2.从应激反应结果出发反向追踪早产儿的应激源,为临床医护工作者对表面麻醉下视网膜激光光凝术治疗和护理采取干预措施、制定规范的护理常规提供依据。
3.通过实验室检测与临床监测的方法,本研究较系统地认识了视网膜激光光凝术治疗这种“微小刺激”在治疗护理过程中的安全隐患,为其他临床医护工作者进行相关研究提供参考。
Background:
Preterm infants refer to live-born babies who are born before37full weeks; neonates are the babies aged from born to28days and this period is the stage that they just live outside from the womb and are still in adaptive state. Neonates in this period are vulnerable compared with adults because of the immature functions of all system organs, hypo-immunity and the weak thermoregulatory function. However, the development of organs in premature newborns lags far behind and their survival rate decreases seriously. If various noxious stimulations such as trauma, blood loss, hypoxia, pain, hot and cold, fear, strenuous exercise, acute infection, operation anesthesia and so on triggering changes of all kinds of functions and metabolic processes affect preterm newborns at neonate stage, a wide range of responses in the body will be triggered as well, including those of nervous system, endocrine system, immune system, the occurrence of stress-induced apoptosis, etc, and these stress responses can even be a threat to lives of premature newborns. As clinicians, we should make an utmost effort to perform the treatment and the care of primary diseases for the infants as well as the prevention of stress responses described above.
Over the years, stress responses of infants during surgeries are concerned. Major surgeries of infants will be carried out after general anesthesia implemented under the premise of stable vital signs and it can reduce stress responses as well as the degree of danger they face will decrease. But the stress responses generating from tiny stimulus are neglected. For the case of preterm newborns, even tiny stimulus will cause serious stress responses because of their poor general conditions, immature development of all systems and fragile lives.
Retinopathy of prematurity (ROP) is a common ophthalmocace threatening the vision of newborns and it perhaps will have serious impacts on the quality of their lives in the future. To implement the ROP screening and laser treatment timely is a key to avoid ROP blindness. Scholars at home and abroad recognize that general or topical anesthesia has different levels of risks regardless of which anesthesia method was used, because objects of ROP laser photocoagulation treatment are preterm infants whose organs develop immaturely. In practice, our hospital give topical anesthesia to majority of infants with ROP in the laser treatment. Although most infants are stable during the treatment, some infants still have abnormal conditions during or after the treatment. So, what is the root of these problems happening in general conditions of the infants with ROP? Whether preterm infants will have stress responses or not during the laser treatment, why and what kind of stress responses will be produced? Clinically, we should prevent and relieve the stress responses through the more targeted measures in order to insure safety of infants's lives during the treatment, however, the related report is seldom at home and abroad.
The neural pathway of pain sense has developed completely in fetal period according to numerous studies both here and abroad in recent years. Therefore, the babies can sense pain after born even can the preterm infants. However, preterm infants are more sensitive to pain than older infants. Anand and colleagues suggested that pain was newborns'potential characteristic and signal system of tissue damages during early ontogeny, and they recognized that the physiological and behavioral responses of pain in neonatal period could be indexes of effective pain assessments instead of self-reports. Although infants can not describe pain degrees because of the younger age or other reasons, there have been related reports using the visual analogue scale (VAS) which is international commonly used to assess pain degrees.
Mahta and colleagues studied on pain during different methods of ROP screening with76preterm infants assigned into tow groups and results revealed that eye speculums caused the highest pain degree of infants no matter what screening method was used. Dhaliwal and colleagues assessed pain of40preterm infants during ROP screening with PIPP scale and results revealed that infants had the same scores when eye speculums were used no matter in indirect ophthalmoscope examination or direct retinal camera examination. Their studies suggested that the eyelid speculum, rather than the examination method, contributed most to the pain.
Mukherjee and coworkers assessed stresses generating from direct retinal camera examination and indirect ophthalmoscope examination of86preterm infants with cardiopulmonary indexes and they recorded heart rate, oxygen saturation, respiratory rate and mean blood pressure before, during and1hour after the examination. The statistical results revealed that heart rate and respiratory rate were the highest in indirect ophthalmoscope examination.
Retinal laser photocoagulation treatment seems just a "tiny stimulus", but adult patients with diabetic retinopathy have pain during panretinal photocoagulation. The degree of this kind of pain will increase with the severity of retinopathy and the pain of patients in proliferative phase is heavier than patients in non-proliferative phase. However, whether retinal laser photocoagulation treatment will lead to stress responses of preterm infants or not has not been reported. This makes clinicians lack anticipations of safety risks of the treatment and lack scientific evidences for early interventions aimed at infants.
At present, there are nursing routine of surgeries, but nursing care programs of retinal laser photocoagulation treatment under topical anesthesia are made by each hospital on their own and there is no uniform and standardized nursing routine; however, clinicians are easy to ignore monitoring of infants who are under topical anesthesia but in waking state and it may make abnormal conditions defiladed as well as clinicians not detect those in time, leading to occurrence of medical negligence.
Therefore, this study applied the retinal laser photocoagulation treatment under topical anesthesia as the model of "tiny stimulus" to explore whether retinal laser photocoagulation treatment under topical anesthesia would trigger stress responses in preterm infants or not to a more comprehensive perspective based on combination of laboratory testing and clinical monitoring, and comprehend safety risks of the treatment. It provided scientific evidences to clinical healthcare assistants to take targeted interventions aiming to avoid the occurrence of serious medical negligence and provided references to clinical healthcare assistants to conduct similar studies on "tiny stimulus" in the future as well.
Objectives:
1.The study focused on laboratory testing and comprehended changes of related biochemical indexes in the blood of preterm infants receiving retinal laser photocoagulation treatment under topical anesthesia at different time before and after the treatment. It explored whether retinal laser photocoagulation treatment therapy under topical anesthesia would trigger stress responses in preterm infants or not to a scientific perspective.
2.To combine the clinical monitoring of physiological indicators (HR, SpO2, RR, MAP) of preterm infants during the treatment to explore whether stress responses existed during the treatment or not comprehensively; to analyze reasons producing stress responses and potential safety risks in the laser photocoagulation treatment under topical anesthesia.
3.The study provided scientific evidences to clinical healthcare assistants for developing interventions and nursing routine of retinal laser photocoagulation treatment. It will reduce complication incidence of laser photocoagulation treatment. The infants with ROP can not only acquire safe and opportune treatments, reducing the blinding rate of additional population, but also have improved quality of lives, reducing the burden of family and society.
4.The study provided evidence-based of monitoring and treatment of preterm infants in retinal laser photocoagulation for clinicians, and standardized the nursing procedure.
5.To provide references to other clinical operations similar to "tiny stimulus" through studying on influences of such "tiny stimulus" like retinal laser photocoagulation treatment on preterm infants. It will reduce incidence of medical negligence and the infants's safety of lives can be guaranteed in the treatment with primary diseases.
Methods:
1.To collect2ml venous blood of30preterm infants undergoing retinal laser photocoagulation treatment under topical anesthesia at four time points respectively: quiet state before treatment, the end of treatment,1hour after treatment and24hours after treatment. We measured the concentration changes of7stress related biochemical indexes in blood such as dopamine, norepinephrine, epinephrine, cortisol, adrenocorticotropic hormone, blood glucose and C-reactive protein through laboratory examinations.
2.To monitor30preterm infants receiving retinal laser photocoagulation treatment under topical anesthesia with medical monitoring equipments and recorded changes of heart rate (HR), oxygen saturation of blood (SpO2), respiratory rate (RR) and mean artery pressure (MAP) of at four time points:quiet state before treatment, the end of treatment,1hour after treatment and24hours after treatment. We recorded and calculated changes range of physiological indexes of infants (SpO2, HR, MAP) during laser photocoagulation treatment.
3.Data entry and statistical methods:The data was handed to statistics directly after data collection and the double check was performed. They used SPSS13.0statistical software for data processing. Indexes were described by mean±standard deviation (x±s) and the analysis of variance (ANOVA) for repeated measurement design data was used. In addition, the method of LSD was used for multiple comparisons between groups, α=0.05(two-sided) was the significant level, P<0.05meant differences had statistically significance.
Results:
1. Changes of stress related factors in blood of30infants before and after retinal laser photocoagulation treatment under topical anesthesia:
1.1Levels of dopamine in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), levels of dopamine in infants at the end of treatment and1hour after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
1.2Levels of norepinephrine in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), levels of norepinephrine in infants at the end of treatment and1hour after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
1.3Levels of epinephrine in infants at different time points had statistical significance in comparison among groups with sum (P<0.05),the level of epinephrine in infants at the end of treatment was higher than that in quiet state before treatment with statistical significance(P<0.05);
1.4Levels of cortisol in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), levels of cortisol in infants at the end of treatment and1hour after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
1.5Levels of adrenocorticotropic hormone in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), the level of adrenocorticotropic hormone in infants at the end of treatment was higher than that in quiet state before treatment with statistical significance(P<0.001);
1.6Levels of blood glucose in infants at different time points had statistical significance in comparison among groups with sum(P<0.001),the level of blood glucose in infants at the end of treatment was higher than that in quiet state before treatment with statistical significance(P<0.001);
1.7Levels of C-reactive protein in infants at different time points had no statistical significance in comparison among groups with sum(P>0.05).
2. Changes of physiological indicators of infants before and after retinal laser photocoagulation treatment under topical anesthesia:
2.1Levels of heart rate (HR) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), HR levels of infants at the end of treatment,1hour after treatment and24hours after treatment had statistical significance compared with that in quiet state before treatment(P<0.05);
2.2Levels of mean artery pressure (MAP) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), the MAP level of infants at the end of treatment were higher than that in quiet state before treatment with statistical significance(P<0.001);
2.3Levels of respiratory rate (RR) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), RR levels of infants at the end of treatment,1hour after treatment and24hours after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
2.4Levels of oxygen saturation of blood (SpO2) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), SpO2levels of infants at1hour and24hours after treatment were higher than that in quiet state before treatment with statistical significance (P<0.05).
3. Changes of behavioral and physiological indicators of infants during retinal laser photocoagulation treatment:
3.1Changes of SpO2:SpO2of2infants (6.7%) decreased below80%,1case (3.3%) fluctuated between80%～90%and27cases (90%) contained higher than90%.
3.2Changes of HR and MAP:HR and MAP of2.(6.7%) cases decreased more than20%of those before treatment,13cases (43.3%) increased less than20%of those before treatment and15cases (50%) increased no less than20%of those before treatment.
Conclusions and Implications for Clinicians:
1. Preterm infants in waking state under topical anesthesia had stress responses during retinal laser photocoagulation treatment.
2. The changes of stress related biochemical indexes in blood of preterm infants proved that stress responses existed during the retinal laser photocoagulation treatment.
3. To monitor changes of behavioral and physiological indicators of preterm infants could suggest that stress responses existed.
4. Clinicians should attach importance to monitoring preterm infants receiving retinal laser photocoagulation treatment under topic anesthesia and take interventions in time because of the time limitation of laboratory testing.
5. The change of physiological indexes triggered by stressors provided monitoring and nursing evidences for clinicians. Although preterm infants are in waking state, clinicians can not ignore assessments and monitoring of preterm infants from the beginning to24hours after retinal laser photocoagulation treatment. Nurses should enhance inspection and assessment to prevent infants from excessive external stimulus.
6. Stress responses of preterm infants during retinal laser photocoagulation treatment were induced by coactions of various stressors.
7. Clinicians should pay attention to the influence of stimulus similar to such "tiny stimulus" in retinal laser photocoagulation treatment on preterm infants in clinical work.
Innovation points:
1. It scientifically demonstrated that preterm infants had stress responses during retinal laser photocoagulation treatment under topic anesthesia through both laboratory testing of stress factors in blood and clinical monitoring of physiological indexes of these preterm babies.
2. The study applied results of stress responses to trace back to stressors of preterm infants, and provided evidences to clinical nurses for implementing treatment and nursing interventions of the retinal laser photocoagulation treatment as well as developing standardized nursing routine.
3. The study recognized the safety risks during such "tiny stimulus" like retinal laser treatments through the methods of laboratory testing and clinical monitoring, and provided references for other clinicians conducting the similar related studies on "tiny stimulus".
早产儿是指胎龄在37足周以前出生的活产婴儿；新生儿是指出生后至28天的婴儿,此时期的婴儿刚刚从母亲子宫内来到外界生活,还处在适应期。由于这段时期新生儿各系统脏器功能发育尚未成熟,免疫功能低下,体温调节功能较差,因而与成人相比,生命力脆弱。而新生早产儿,由于各器官发育程度远远落后,生存率大大下降。此时期若机体受到各种伤害性刺激,如创伤、失血、缺氧、疼痛、冷热、恐惧、剧烈运动、急性感染和手术麻醉等,引起机体各种功能和代谢过程的变化,可在全身范围内引起一系列广泛的反应,包括神经系统、内分泌系统、免疫系统的反应及发生应激性细胞凋亡等,而引起的应激反应,甚至可以威胁到新生早产儿的生命安全。作为临床医护工作者,在治疗和护理患儿原发病的同时,应当极力避免这种情况的发生。
多年来,儿童在手术时产生的应激反应一直备受关注。大型儿童外科手术会在患儿生命体征稳定的前提下进行全身麻醉后进行,这使得患儿所受到的应激反应及其所面临的危险程度大大减小。但是,微小程度刺激所引起的应激反应没有得到足够重视。对于新生早产儿而言,由于全身基础情况差,即使受到微小刺激,也可能引起新生早产儿严重的应激反应。
早产儿视网膜病变(retinopathy of prematurity, ROP)是一种较为常见的威胁新生儿视力的眼科疾病,可能严重影响其未来生活质量。及早进行ROP筛查和激光治疗,是避免ROP致盲的关键。由于ROP激光光凝术的对象均是各器官发育尚未成熟的早产儿,国内外学者认识到,无论是采用全身麻醉还是表面麻醉,两种方式均有不同程度的风险存在。实践中,本医院对多数ROP患儿采用在表面麻醉下治疗,虽然多数患儿都完成整个治疗过程,但是,通过观察可以发现,仍然有患儿在治疗中或治疗后全身状况出现异常。那么,这些被诊断为ROP的患儿出现这些问题的根源何在?在表面麻醉下进行ROP激光光凝术的早产儿在治疗中是否会产生应激反应,为何会产生应激反应,会产生怎样的应激反应?临床上,应当如何通过更加具有针对性的干预措施,预防与减轻这种应激反应,从而保证患儿在接受治疗过程中的生命安全,目前相关的研究报道在国内外不多。
近年来国内外研究表明,在胎儿时期感受疼痛的神经传导通路就已发育完善,因此,即使是早产儿,在出生后就已具备感受疼痛的能力。而且,早产儿对疼痛的感受较年长儿更为敏感。Anand等提出,疼痛是新生儿的潜在特质,是个体发育早期的组织损伤信号系统,并且认为新生儿期疼痛的生理和行为反应可替代主观自述而作为有效的评估疼痛的指标。虽然患儿由于年龄小等原因无法对疼痛程度大小进行描述,但已有相关报道,采用国际常用的视觉模拟评分法(visual analogue scale, VAS)对疼痛程度进行评分。
Mahta等将76名早产儿分为两组,使用不同的ROP筛查方法,对早产儿的疼痛情况进行研究,结果表明,无论使用何种ROP筛查方法,开睑器对患儿造成的疼痛是最大的。Dhaliwal等对40名早产儿在ROP筛查时,使用PIPP量表进行疼痛评分,结果显示,使用开睑器时,无论是间接的眼底镜检查还是直接的视网膜照相机检查,婴儿都有相似的疼痛分值。他们的研究共同表明,眼科检查带来的大多数疼痛源于开睑器的使用,而不是检查方式本身的问题。
Mukherjee等用心肺的指标去评估直接的视网膜照相机检查和间接眼底镜检查对86名早产儿造成的刺激,研究记录检查前、检查过程中和检查后1小时的心率、血氧饱和度、呼吸频率和平均血压,统计后发现心率和呼吸频率在间接眼底镜检查中较高。
视网膜激光光凝术治疗看似只是一个“微小刺激”,但成人糖尿病视网膜病变患者在接受全视网膜光凝过程中是有疼痛感的,眼底病变程度越重,患者在激光光凝时的疼痛感也相应更重,增殖期的疼痛感觉重于非增殖期。而有关视网膜激光光凝术治疗是否会导致早产儿产生应激反应的研究尚未见报道。这使得临床工作者在工作中缺乏对该治疗方法安全隐患的预期,也缺乏对患儿进行早期干预的科学依据。
目前,外科、大手术护理均有相应的护理常规,而表面麻醉下行视网膜激光光凝术治疗的护理常规均为各医院自行制定,尚无统一、规范的护理常规；而且,在临床工作中,医护工作者容易忽视对表面麻醉下处于清醒状态患儿的监测,使患儿的异常状况未能被医护人员及时发现,而导致不良医疗事件的发生。
因此,本研究在国内率先以表面麻醉下视网膜激光光凝术治疗为“微小刺激”模型,将实验室检测与临床监测相结合,从科学的角度探讨表面麻醉下视网膜激光光凝术治疗是否会使早产儿产生应激反应,了解该治疗方法存在的安全隐患,为临床医护工作者采取针对性的干预措施提供科学依据,避免严重医疗事故的发生,同时也为临床医护工作者今后进行类似“微小刺激”的研究提供参考。
研究目的：
1.本研究以实验室检测为重点,了解表面麻醉下接受视网膜激光光凝术治疗的早产儿在治疗前后不同时间点血液中应激相关生化指标的变化,从科学的角度探讨表面麻醉下接受视网膜激光光凝术治疗的早产儿在治疗中是否会产生应激反应。
2.结合临床工作中对表面麻醉下视网膜激光光凝术治疗时,早产儿生理指标监测,以更全面的角度探讨在治疗中应激反应存在与否；分析导致表面麻醉下视网膜激光光凝术治疗应激反应产生原因,以及表面麻醉下视网膜激光光凝术治疗存在安全隐患。
3.本研究为临床医护工作者共同制定表面麻醉下视网膜激光光凝术治疗的干预措施与护理常规提供科学依据,将避免或减少激光光凝术并发症的发生,既可以使ROP患儿能够获得安全、及时的治疗,从而减少新增人口的致盲率；又使患儿的生活质量得到提高,减轻家庭、社会的负担。
4.本研究对医护人员如何为表面麻醉下视网膜激光光凝术治疗的早产儿监测及治疗提供循证依据,规范护理操作流程。
5.通过研究视网膜激光光凝术治疗这种“微小刺激”对早产儿造成的影响,为临床其他类似的“微小刺激”操作提供参照,减少医疗意外事故的发生,在治疗早产儿原发病的同时,使患儿的生命安全得到保障。
研究方法：
1.对表面麻醉下进行视网膜激光光凝术的早产儿,分别于治疗前安静状态、治疗结束时、治疗后1h、治疗后24h抽取其静脉血2ml,采用实验室检查的方法,检测血液中多巴胺、去甲肾上腺素、肾上腺素、皮质醇、促肾上腺皮质激素(adreno-cortico-tropic-hormone, ACTH)、血糖、C反应蛋白(C-reactive protein, CRP)7个与应激相关生化指标的浓度变化。
2.使用心电监护仪对表面麻醉下接受视网膜激光光凝术的早产儿进行监测,记录视网膜激光光凝术治疗前安静状态、治疗结束时、治疗后1h、治疗后24h其心率(heart rate, HR)、血氧饱和度(oxygen saturation of blood, SpO2)、呼吸频率(respiratory rate, RR)、平均动脉压(mean artery pressure, MAP)的变化；记录并统计在激光光凝术治疗过程中早产儿生理指标(SPO2、HR、 MAP)的变化幅度。
3.数据录入及统计学方法：研究数据收集后直接交给数据统计人员,录入后进行双人核对。采用SPSS13.0统计软件进行数据处理,各检测指标以均数±标准差(x±s)表示,采用重复测量设计的方差分析,组间多重比较采用LSD法,以α=0.05(双侧)为检验水准,P<0.05时差异有统计学意义。
结果：
1.30例表面麻醉下视网膜激光光凝术治疗前后患儿血液中应激相关生化指标变化：
1.1患儿不同时间点多巴胺水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h患儿多巴胺的水平高于治疗前安静状态,差异有统计学意义(P<0.05)；
1.2患儿不同时间点去甲肾上腺素水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h患儿去甲肾上腺素的水平高于治疗前安静状态,差异有统计学意义(P<0.05)；
1.3患儿不同时间点肾上腺素水平组间总的比较差异有统计学意义(P<0.05),治疗结束时肾上腺素水平高于治疗前安静状态,差异有统计学意义(P<0.05)：
1.4患儿不同时间点皮质醇水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h患儿皮质醇的水平高于治疗前安静状态,差异有统计学意义(P<0.05)；
1.5患儿不同时间点ACTH水平组间总的比较差异有统计学意义(P<0.001),治疗结束时患儿ACTH的水平高于治疗前安静状态,差异有统计学意义(P<0.001)；
1.6患儿不同时间点血糖水平组间总的比较差异有统计学意义(P<0.001),治疗结束时患儿血糖的水平高于治疗前安静状态,差异有统计学意义(P<0.001)；
1.7患儿不同时间点CRP水平组间总的比较差异无统计学意义(P>0.05)。
2.表面麻醉下视网膜激光光凝术治疗前后患儿生理指标的变化：
2.1患儿不同时间点HR水平组间总的比较差异有统计学意义(P<0.001),治疗结束时、治疗后1h、治疗后24h患儿HR的变化与治疗前安静状态相比,差异有统计学意义(P<0.05)：
2.2患儿不同时间点MAP水平组间总的比较差异有统计学意义(P<0.001),治疗结束时患儿MAP的水平高于治疗前安静状态,差异具有统计学意义(P<0.001))；
2.3患儿不同时间点RR水平组间总的比较差异有统计学意义(P<0.001)；治疗结束时、治疗后1h、治疗后24h患儿RR的水平均高于治疗前安静状态,差异有统计学意义(P<0.05)；
2.4患儿不同时间点Sp02水平组间总的比较差异有统计学意义(P<0.001)；治疗后1h、治疗后24h SpO2高于治疗前安静状态下的水平,差异有统计学意义(P<0.05)
3.视网膜激光光凝术治疗过程中患儿生理指标的变化
3.1Sp02的变化：2例(6.7%)患儿Sp02降至80%以下,1例(3.3%)患儿在80%-90%水平,27例(90%)患儿Sp02均维持在90%以上。
3.2HR与MAP的变化：2例(6.7%)患儿的HR与MAP的下降幅度≥治疗前水平20%,13例(43.3%)患儿的升降幅度<治疗前水平20%,15例(50%)患儿的HR与MAP的升高幅度≥治疗前水平的20%。
结论及对临床工作者的提示：
1.在表面麻醉下进行ROP激光光凝术治疗的早产儿,治疗过程中会产生应激反应。
2.通过实验室检测早产儿血液中应激相关生化指标的变化,可以证明其在激光光凝术治疗过程中存在应激反应。
3.通过临床监测早产儿生理指标的改变能反映视网膜激光光凝术治疗过程中应激反应的存在。
4.由于实验室检测在时效方面的局限性,临床医护工作者应当重视对表面麻醉下视网膜激光光凝术早产儿的临床监测并及时采取应对措施。
5.应激源所引起的生理指标变化为临床医护人员的监测及护理提供依据。虽然表面麻醉下的早产儿一直处于清醒状态,临床医护工作者绝对不能忽视视网膜激光光凝术治疗开始至治疗后24h这段时间内对早产儿的评估与监测,尤其应当注意HR与RR的变化,护士应加强巡视和评估,尽量避免早产儿再受到外界过多的刺激。
6.视网膜激光光凝术治疗中早产儿的应激反应是由多种应激源共同作用所导致的。
7.在临床工作中,应重视类似于视网膜激光光凝术这种“微小刺激”对早产儿造成的影响。
创新点：
1.从对血液中应激因子的实验室检测以及对其生理指标的监测结果两个方面的研究,科学论证了在表面麻醉下接受早产儿视网膜激光光凝术治疗时患儿会产生应激反应。
2.从应激反应结果出发反向追踪早产儿的应激源,为临床医护工作者对表面麻醉下视网膜激光光凝术治疗和护理采取干预措施、制定规范的护理常规提供依据。
3.通过实验室检测与临床监测的方法,本研究较系统地认识了视网膜激光光凝术治疗这种“微小刺激”在治疗护理过程中的安全隐患,为其他临床医护工作者进行相关研究提供参考。
Background:
Preterm infants refer to live-born babies who are born before37full weeks; neonates are the babies aged from born to28days and this period is the stage that they just live outside from the womb and are still in adaptive state. Neonates in this period are vulnerable compared with adults because of the immature functions of all system organs, hypo-immunity and the weak thermoregulatory function. However, the development of organs in premature newborns lags far behind and their survival rate decreases seriously. If various noxious stimulations such as trauma, blood loss, hypoxia, pain, hot and cold, fear, strenuous exercise, acute infection, operation anesthesia and so on triggering changes of all kinds of functions and metabolic processes affect preterm newborns at neonate stage, a wide range of responses in the body will be triggered as well, including those of nervous system, endocrine system, immune system, the occurrence of stress-induced apoptosis, etc, and these stress responses can even be a threat to lives of premature newborns. As clinicians, we should make an utmost effort to perform the treatment and the care of primary diseases for the infants as well as the prevention of stress responses described above.
Over the years, stress responses of infants during surgeries are concerned. Major surgeries of infants will be carried out after general anesthesia implemented under the premise of stable vital signs and it can reduce stress responses as well as the degree of danger they face will decrease. But the stress responses generating from tiny stimulus are neglected. For the case of preterm newborns, even tiny stimulus will cause serious stress responses because of their poor general conditions, immature development of all systems and fragile lives.
Retinopathy of prematurity (ROP) is a common ophthalmocace threatening the vision of newborns and it perhaps will have serious impacts on the quality of their lives in the future. To implement the ROP screening and laser treatment timely is a key to avoid ROP blindness. Scholars at home and abroad recognize that general or topical anesthesia has different levels of risks regardless of which anesthesia method was used, because objects of ROP laser photocoagulation treatment are preterm infants whose organs develop immaturely. In practice, our hospital give topical anesthesia to majority of infants with ROP in the laser treatment. Although most infants are stable during the treatment, some infants still have abnormal conditions during or after the treatment. So, what is the root of these problems happening in general conditions of the infants with ROP? Whether preterm infants will have stress responses or not during the laser treatment, why and what kind of stress responses will be produced? Clinically, we should prevent and relieve the stress responses through the more targeted measures in order to insure safety of infants's lives during the treatment, however, the related report is seldom at home and abroad.
The neural pathway of pain sense has developed completely in fetal period according to numerous studies both here and abroad in recent years. Therefore, the babies can sense pain after born even can the preterm infants. However, preterm infants are more sensitive to pain than older infants. Anand and colleagues suggested that pain was newborns'potential characteristic and signal system of tissue damages during early ontogeny, and they recognized that the physiological and behavioral responses of pain in neonatal period could be indexes of effective pain assessments instead of self-reports. Although infants can not describe pain degrees because of the younger age or other reasons, there have been related reports using the visual analogue scale (VAS) which is international commonly used to assess pain degrees.
Mahta and colleagues studied on pain during different methods of ROP screening with76preterm infants assigned into tow groups and results revealed that eye speculums caused the highest pain degree of infants no matter what screening method was used. Dhaliwal and colleagues assessed pain of40preterm infants during ROP screening with PIPP scale and results revealed that infants had the same scores when eye speculums were used no matter in indirect ophthalmoscope examination or direct retinal camera examination. Their studies suggested that the eyelid speculum, rather than the examination method, contributed most to the pain.
Mukherjee and coworkers assessed stresses generating from direct retinal camera examination and indirect ophthalmoscope examination of86preterm infants with cardiopulmonary indexes and they recorded heart rate, oxygen saturation, respiratory rate and mean blood pressure before, during and1hour after the examination. The statistical results revealed that heart rate and respiratory rate were the highest in indirect ophthalmoscope examination.
Retinal laser photocoagulation treatment seems just a "tiny stimulus", but adult patients with diabetic retinopathy have pain during panretinal photocoagulation. The degree of this kind of pain will increase with the severity of retinopathy and the pain of patients in proliferative phase is heavier than patients in non-proliferative phase. However, whether retinal laser photocoagulation treatment will lead to stress responses of preterm infants or not has not been reported. This makes clinicians lack anticipations of safety risks of the treatment and lack scientific evidences for early interventions aimed at infants.
At present, there are nursing routine of surgeries, but nursing care programs of retinal laser photocoagulation treatment under topical anesthesia are made by each hospital on their own and there is no uniform and standardized nursing routine; however, clinicians are easy to ignore monitoring of infants who are under topical anesthesia but in waking state and it may make abnormal conditions defiladed as well as clinicians not detect those in time, leading to occurrence of medical negligence.
Therefore, this study applied the retinal laser photocoagulation treatment under topical anesthesia as the model of "tiny stimulus" to explore whether retinal laser photocoagulation treatment under topical anesthesia would trigger stress responses in preterm infants or not to a more comprehensive perspective based on combination of laboratory testing and clinical monitoring, and comprehend safety risks of the treatment. It provided scientific evidences to clinical healthcare assistants to take targeted interventions aiming to avoid the occurrence of serious medical negligence and provided references to clinical healthcare assistants to conduct similar studies on "tiny stimulus" in the future as well.
Objectives:
1.The study focused on laboratory testing and comprehended changes of related biochemical indexes in the blood of preterm infants receiving retinal laser photocoagulation treatment under topical anesthesia at different time before and after the treatment. It explored whether retinal laser photocoagulation treatment therapy under topical anesthesia would trigger stress responses in preterm infants or not to a scientific perspective.
2.To combine the clinical monitoring of physiological indicators (HR, SpO2, RR, MAP) of preterm infants during the treatment to explore whether stress responses existed during the treatment or not comprehensively; to analyze reasons producing stress responses and potential safety risks in the laser photocoagulation treatment under topical anesthesia.
3.The study provided scientific evidences to clinical healthcare assistants for developing interventions and nursing routine of retinal laser photocoagulation treatment. It will reduce complication incidence of laser photocoagulation treatment. The infants with ROP can not only acquire safe and opportune treatments, reducing the blinding rate of additional population, but also have improved quality of lives, reducing the burden of family and society.
4.The study provided evidence-based of monitoring and treatment of preterm infants in retinal laser photocoagulation for clinicians, and standardized the nursing procedure.
5.To provide references to other clinical operations similar to "tiny stimulus" through studying on influences of such "tiny stimulus" like retinal laser photocoagulation treatment on preterm infants. It will reduce incidence of medical negligence and the infants's safety of lives can be guaranteed in the treatment with primary diseases.
Methods:
1.To collect2ml venous blood of30preterm infants undergoing retinal laser photocoagulation treatment under topical anesthesia at four time points respectively: quiet state before treatment, the end of treatment,1hour after treatment and24hours after treatment. We measured the concentration changes of7stress related biochemical indexes in blood such as dopamine, norepinephrine, epinephrine, cortisol, adrenocorticotropic hormone, blood glucose and C-reactive protein through laboratory examinations.
2.To monitor30preterm infants receiving retinal laser photocoagulation treatment under topical anesthesia with medical monitoring equipments and recorded changes of heart rate (HR), oxygen saturation of blood (SpO2), respiratory rate (RR) and mean artery pressure (MAP) of at four time points:quiet state before treatment, the end of treatment,1hour after treatment and24hours after treatment. We recorded and calculated changes range of physiological indexes of infants (SpO2, HR, MAP) during laser photocoagulation treatment.
3.Data entry and statistical methods:The data was handed to statistics directly after data collection and the double check was performed. They used SPSS13.0statistical software for data processing. Indexes were described by mean±standard deviation (x±s) and the analysis of variance (ANOVA) for repeated measurement design data was used. In addition, the method of LSD was used for multiple comparisons between groups, α=0.05(two-sided) was the significant level, P<0.05meant differences had statistically significance.
Results:
1. Changes of stress related factors in blood of30infants before and after retinal laser photocoagulation treatment under topical anesthesia:
1.1Levels of dopamine in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), levels of dopamine in infants at the end of treatment and1hour after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
1.2Levels of norepinephrine in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), levels of norepinephrine in infants at the end of treatment and1hour after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
1.3Levels of epinephrine in infants at different time points had statistical significance in comparison among groups with sum (P<0.05),the level of epinephrine in infants at the end of treatment was higher than that in quiet state before treatment with statistical significance(P<0.05);
1.4Levels of cortisol in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), levels of cortisol in infants at the end of treatment and1hour after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
1.5Levels of adrenocorticotropic hormone in infants at different time points had statistical significance in comparison among groups with sum(P<0.001), the level of adrenocorticotropic hormone in infants at the end of treatment was higher than that in quiet state before treatment with statistical significance(P<0.001);
1.6Levels of blood glucose in infants at different time points had statistical significance in comparison among groups with sum(P<0.001),the level of blood glucose in infants at the end of treatment was higher than that in quiet state before treatment with statistical significance(P<0.001);
1.7Levels of C-reactive protein in infants at different time points had no statistical significance in comparison among groups with sum(P>0.05).
2. Changes of physiological indicators of infants before and after retinal laser photocoagulation treatment under topical anesthesia:
2.1Levels of heart rate (HR) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), HR levels of infants at the end of treatment,1hour after treatment and24hours after treatment had statistical significance compared with that in quiet state before treatment(P<0.05);
2.2Levels of mean artery pressure (MAP) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), the MAP level of infants at the end of treatment were higher than that in quiet state before treatment with statistical significance(P<0.001);
2.3Levels of respiratory rate (RR) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), RR levels of infants at the end of treatment,1hour after treatment and24hours after treatment were higher than that in quiet state before treatment with statistical significance(P<0.05);
2.4Levels of oxygen saturation of blood (SpO2) of infants at different time points had statistical significance in comparison among groups with sum(P<0.001), SpO2levels of infants at1hour and24hours after treatment were higher than that in quiet state before treatment with statistical significance (P<0.05).
3. Changes of behavioral and physiological indicators of infants during retinal laser photocoagulation treatment:
3.1Changes of SpO2:SpO2of2infants (6.7%) decreased below80%,1case (3.3%) fluctuated between80%～90%and27cases (90%) contained higher than90%.
3.2Changes of HR and MAP:HR and MAP of2.(6.7%) cases decreased more than20%of those before treatment,13cases (43.3%) increased less than20%of those before treatment and15cases (50%) increased no less than20%of those before treatment.
Conclusions and Implications for Clinicians:
1. Preterm infants in waking state under topical anesthesia had stress responses during retinal laser photocoagulation treatment.
2. The changes of stress related biochemical indexes in blood of preterm infants proved that stress responses existed during the retinal laser photocoagulation treatment.
3. To monitor changes of behavioral and physiological indicators of preterm infants could suggest that stress responses existed.
4. Clinicians should attach importance to monitoring preterm infants receiving retinal laser photocoagulation treatment under topic anesthesia and take interventions in time because of the time limitation of laboratory testing.
5. The change of physiological indexes triggered by stressors provided monitoring and nursing evidences for clinicians. Although preterm infants are in waking state, clinicians can not ignore assessments and monitoring of preterm infants from the beginning to24hours after retinal laser photocoagulation treatment. Nurses should enhance inspection and assessment to prevent infants from excessive external stimulus.
6. Stress responses of preterm infants during retinal laser photocoagulation treatment were induced by coactions of various stressors.
7. Clinicians should pay attention to the influence of stimulus similar to such "tiny stimulus" in retinal laser photocoagulation treatment on preterm infants in clinical work.
Innovation points:
1. It scientifically demonstrated that preterm infants had stress responses during retinal laser photocoagulation treatment under topic anesthesia through both laboratory testing of stress factors in blood and clinical monitoring of physiological indexes of these preterm babies.
2. The study applied results of stress responses to trace back to stressors of preterm infants, and provided evidences to clinical nurses for implementing treatment and nursing interventions of the retinal laser photocoagulation treatment as well as developing standardized nursing routine.
3. The study recognized the safety risks during such "tiny stimulus" like retinal laser treatments through the methods of laboratory testing and clinical monitoring, and provided references for other clinicians conducting the similar related studies on "tiny stimulus".
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