The Infancy of Infant Pain Research: The Experimental Origins of Infant Pain Denial

Skepticism toward infant pain characterized much of 20th century research and clinical practice, with infant surgery routinely conducted with minimal or no anesthesia into the 1980s. This paper offers a historical exploration of how this view became common by reviewing and analyzing the experimental infant pain research of the 19th and early 20th centuries that contributed to the development of infant pain denial. These experiments used pinprick and electric shock, and the results were generally interpreted as evidence of infants’ underdeveloped pain perception, attributed to their lack of brain maturation. Even clear responses to noxious stimuli were often dismissed as reflex responding. Later these experimental findings were used by anesthesiologists to support the lessened use of anesthesia for infants. Based on the reviewed literature, this paper suggests that 4 interrelated causes contributed to the denial of infant pain: the Darwinian view of the child as a lower being, extreme experimental caution, the mechanistic behaviorist perspective, and an increasing emphasis on brain and nervous system development. Ultimately this history can be read as a caution to modern researchers to be aware of their own biases, the risks of null hypothesis testing, and a purely mechanistic view of infants.PerspectiveThis article reviews the history of 19th and early 20th century infant pain research, tracing how the widely accepted belief that infants could not feel pain developed in the period prior to the growing acceptance of infant pain. Four interrelated causes are posited to help explain the tolerance of infant pain denial until recent times.     

A history of the training of asylum nurses

The national training scheme for asylum attendants, devised in the late 19th century, did not arise ex nihilo Several philanthropic and imaginative madhouse keepers of the previous century had understood the link between successful treatment of lunatics and the quality of staff who cared for them They had therefore aimed to recruit a 'good class' of person to work in their institutions, and to create an environment which would tend towards the civilization of the patients A few even entertained the notion that training attendants would enhance their ability to understand and care for those in their charge Training received increasing attention in both medical and political circles throughout the 19th century until a national scheme was inaugurated in 1891 The scheme achieved only a modest success in that, while it drew upon the undoubted enthusiasm of those who trained under it, it did not enhance the attendants' career opportunities or their pay once they had qualified Training as a means of solving management problems was doomed to failure, and widespread dissatisfaction amongst asylum nurses erupted during the 1920s, only 30 years after the scheme had started     

Seek and You Shall Find—But Then What Do You Do? Cold Agglutinins in Cardiopulmonary Bypass and a Single-Center Experience With Cold Agglutinin Screening Before Cardiac Surgery

Cardiopulmonary bypass (CPB) during cardiac surgery can involve deliberate hypothermia of the systemic (22-36°C) and coronary circulations (as low as 8-12°C). Adverse sequelae of cold-active antibodies have been feared and reported under such conditions, and some centers thus elect to screen for cold agglutinins before CPB. We reviewed the literature on cold agglutinins in cardiac surgery and described the yields and effects of cold agglutinin screening (CAS) in 14 900 cardiac surgery patients undergoing CPB over 8 years at a single institution. Cold agglutinin screening was positive in 47 cases (0.3%), at an annual testing cost of $17 000 CAD. The response of the surgical team to the preoperative discovery of a cold agglutinin was variable, with CPB modified to avoid hypothermia in approximately one-third of cases. In patients discovered to have a positive CAS, postoperative intensive care unit and hospital length of stay were marginally increased (54.6 vs 42.8 hours, P = .02; 7 [6-14] vs 7 [5-9] days, P = .04). However, the composite of mortality or severe morbidity (stroke, myocardial infarction, dialysis, low output syndrome, sepsis, and deep vein thrombosis) was not significantly different (14.9% vs 9.2%, P = .2). Antibody verification found that only 43% of positive CAS patients had true cold agglutinins (20 patients). Furthermore, the rate of adverse events was low in both CAS-positive and true-positive cold agglutinin patients undergoing CPB and cardiac surgery. Finally, modification of CPB to attenuate hypothermia did not decrease adverse events. Based upon historical and local data, preclinical CAS is cost-substantial and nonspecific. Cold agglutinin screening does not promote an algorithm of care that meaningfully improves patient CPB outcomes.     

Circadian rhythmicity and homeostatic stability in thermoregulation

Stability and circadian variation in core body temperature (Tc) were believed to be homeostatic responses until well into the 20th century. Defense of a narrow thermoneutral range was well documented, whereas circadian oscillations were attributed to episodic biochemical and environmental stimuli or chronological stressors in life routines. Research in thermal physiology has illuminated several of the "black boxes" in the understanding of temperature regulation, and advances in chronobiology have shattered old paradigms. While these discoveries are still evolving, existing information provides valuable clues about physiological responses to heat loss or over-heating that could improve clinical assessment and intervention. Discoveries that circadian rhythm of Tc is regulated by an endogenous "clock" and is remarkably stable have helped to make it the most widely used circadian indicator. More recently, Tc was found to exert its own cyclic rhythm under free-running conditions. While some investigators claim that circadian and homeostatic processes are independent, there are conditions in which clinical distinctions are less clear. This overview reviews contemporary scientific findings about circadian and homeostatic processes in thermoregulation. Examples are drawn from human and animal research. Physiological responses and mechanisms are explained in relation to their relevance to clinical treatment or health care. Gaps in existing research and application are discussed.     

兔心肺复苏后经腹腔诱导亚低温的研究

目的 探讨兔心肺复苏后经腹腔灌注低温液体能否诱导亚低温并评价其安全性.方法 实验一:15只成年新西兰兔依据灌注首剂4℃低温液体剂量的不同分为30,40,60,80和100 mL/ks5组,选择鼓膜温度卜降迅速、稳定的一组连接腹腔灌流装置(专利号Z1200820201265)维持亚低温12h,随后进行复温,并以该组的首剂剂量作为实验二的首剂量.观察血浆生化指标的变化和肝、小肠、肾组织的损伤情况.实验二:12只成年新西兰兔,用电致颤的方式建立心肺复苏(CPR)模型,自主循环恢复(ROSC)后向腹腔内灌入首剂4℃低温液体,达到目标温度后连接腹腔灌流装置维持业低温12h,观察生化指标的变化.腹腔灌液前后生化指标的比较用配对t检验,P<0.05为差异具有统计学意义.结果 实验一:兔腹腔内灌注80 mL/kg低温液体后鼓膜温度(30±2.00)min达到目标温度,通过腹腔灌流装置能稳定维持亚低温和缓慢复温,腹腔灌液后没有出现生化指标的紊乱和造成肝、肾、肠的组织学损伤.实验二:ROSC后兔腹腔内灌注80mL/kg 4℃低温液体后鼓膜温度(26.00±6.99)min达到目标温度,腹腔温度不足10min达到甘标温度,ROSC后腹腔内灌注4℃低温液体没有出现生化指标的紊乱.结论 兔心肺复苏后经腹腔灌注低温液体能安全、快速诱导亚低温.     

The Evolution of Abdominal Compression in Cardiopulmonary Resuscitation

Objective: To review the history of external abdominal compression as an adjunct to cardiopulmonary resuscitation (CPR), tracking the development of five major themes over the course of the 20th century: 1) augmentation of peripheral resistance by physical means, 2) risk of hepatic injury with abdominal compression, 3) counterpulsation vs sustained compression, 4) the abdominal pump mechanism, and 5) contact compression techniques.
Methods: Literature retrieved from successive MEDLINE English-language searches was reviewed with a special emphasis on work and concepts highlighted by participants at the First Purdue Conference on Interposed Abdominal Compression-CPR, September 1992.
Results: External abdominal compression of one form or another has been studied as a means of resuscitation by many investigators throughout the 20th century. Experimental and clinical studies have shown generally consistent evidence of hemodynamic augmentation by abdominal compression during various forms of CPR. Recent advances include a modified theoretical understanding of hemodynamic mechanisms and demonstration of clinical potential in humans. Inconsistencies in published results may be due to differences in mechanical techniques of abdominal compression. Based on these studies, a modified manual technique for "contact compression" of the abdominal aorta is recommended.
Conclusions: A technique for left-of-center, angled compression of the abdominal aorta against the crest of the spine is recommended. Further well-supervised and controlled clinical trials using this standardized technique are warranted as a prelude to more widespread clinical application of abdominal compression in CPR.     

Liquid ventilation with perfluorocarbons facilitates resumption of spontaneous circulation in a swine cardiac arrest model

BACKGROUND: Induced external hypothermia during ventricular fibrillation (VF) improves resuscitation outcomes. Our objectives were twofold (1) to determine if very rapid hypothermia could be achieved by intrapulmonary administration of cold perfluorocarbons (PFC), thereby using the lungs as a vehicle for targeted cardiopulmonary hypothermia, and (2) to determine if this improved resuscitation success. METHODS: Part 1: Nine female swine underwent static intrapulmonary instillation of cold perfluorocarbons (PFC) during electrically induced VF. Part 2: Thirty-three female swine in VF were immediately ventilated via total liquid ventilation (TLV) with pre-oxygenated cold PFC (-15 degrees C) or warm PFC (33 degrees C), while control swine received no ventilation during VF. All swine in both Parts 1 and 2 underwent VF arrest for 11 min, then defibrillation, ventilation and closed chest massage until resumption of spontaneous circulation (ROSC). The endpoint was continued spontaneous circulation for 1h without pharmacologic support. RESULTS: Static intrapulmonary instillation of cold PFC achieved rapid cardiopulmonary hypothermia; pulmonary artery (PA) temperature of 33.5+/-0.2 degrees C was achieved by 10 min. Nine of 9 achieved ROSC. Hypothermia was achieved faster using TLV: at 6 min VF, cold TLV temperature was 32.9+/-0.4 degrees C vs. cold static instillation temperature 34.3+/-0.2 degrees C. Nine of 11 cold TLV swine achieved ROSC for 1h vs. 3 of 11 control swine (p=0.03). Warm PFC also appeared to be beneficial, with a trend toward greater achievement of ROSC than control (ROSC; warm PFC 8 of 11 vs. control 3 of 11, p=0.09). CONCLUSION: Targeted cardiopulmonary intra-arrest moderate hypothermia was achieved rapidly by static intrapulmonary administration of cold PFC and more rapidly by total liquid ventilation with cold PFC; resumption of spontaneous circulation was facilitated. Warm PFC showed a trend toward facilitating ROSC.     

Inadvertent hypothermia prevention: the anaesthetic nurses' role

Up to 90% of patients experience hypothermia perioperatively. Inadvertent hypothermia can have a profound physiological effect on the body, varying from mild vasoconstriction and feeling cold to cardiac arrest and death. Anaesthesia, general or regional, increases the risk as the normal protective reflexes such as shivering are absent, particularly when muscle relaxants are used. The very young and the elderly are particularly vulnerable. Preoperative assessment is essential. The greatest reduction in temperature occurs in the first hour of surgery, as a result of patient exposure, skin disinfection with cold fluids, inhalation of cold volatile gases and the administration of cold intravenous fluids, as well as exposure to cool theatre temperatures. If the theatre temperature drops below 21 degrees C, all patients will develop hypothermia. Patients lose heat through radiation, convention and conduction, with conduction having the greatest effect. Forced air warmers such as the Bair Hugger are the most effective means of preventing and treating heat loss. They should be used routinely although their contribution to infection also needs to be considered. Nurses should be aware of the risks of hypothermia so that modes of prevention can be employed to minimize the risks of inadvertent hypothermia.     

Clinical informatics in critical care

Health care information systems have the potential to enable better care of patients in much the same manner as the widespread use of the automobile and telephone did in the early 20th century. The car and phone were rapidly accepted and embraced throughout the world when these breakthroughs occurred. However, the automation of health care with use of computerized information systems has not been as widely accepted and implemented as computer technology use in all other sectors of the global economy. In this article, the authors examine the need, risks, and rewards of clinical informatics in health care as well as its specific relationship to critical care medicine.     

Accidental Hypothermia In Man

Much is yet unknown on the pathogenesis of accidental hypothermia in man. Data are mainly derived from comparative physiological studies in mammals, but some knowledge has been obtained from direct clinical observation and the experience gained with induced hypothermia in anesthesia. The usual criteria of death do not apply to hypothermia and awareness of the altered physiology under such conditions is essential for quick and effective treatment. There appears to be a shift in rewarming procedures from superficial rewarming by conservative methods to the more aggressive forms of central rewarming. Despite practical limitations the latter methods, especially peritoneal dialysis, are more effective and decrease mortality.     

Acute and chronic hypothermia in a man with spinal cord injury: environmental and pharmacologic causes

It is well known that people with spinal cord injuries can develop hypothermia when exposed to an unusually cold environment. Hypothermia can also develop during inpatient rehabilitation, particularly as a side effect of certain medications. We present a patient with C4 incomplete spinal cord injury whose core body temperature was chronically subnormal, and who developed acute hypothermia on several occasions during inpatient rehabilitation. The results of tests of his autonomic function were abnormal. Acute hypothermia (core temperature approximately 34C) was induced when he was challenged with nifedipine. The serum level of phenytoin became elevated to toxic levels during two episodes of acute hypothermia, but the serum level of carbamazepine did not change appreciably. This case demonstrates that people with spinal cord injuries are at risk for hypothermia, that hypothermia can be induced by nifedipine, and that significant thermal challenges can occur during routine inpatient rehabilitation. In addition, hypothermia appears to affect the metabolism of phenytoin.     

Reactions to cold exposure emphasize the need for weather protection in prehospital care: an experimental study

INTRODUCTION: Exposure to cold temperature is a serious but often neglected problem in prehospital care. It not only is an uncomfortable, subjective experience, but it also can cause severe disturbances in vital functions, gradually leading to hypothermia. OBJECTIVE: The aim of this study was to examine healthy subjects' physiological and subjective reactions to cold exposure (30 minutes at -5 degrees C in the a climatic chamber) while they were lying in a protective covering. METHODS: Healthy volunteers (n = 20) participated in the experiment, which consisted of a 10-minute stabilization period of vital functions at room temperature (23 degrees C), 30 minutes of cold exposure (-5 degrees C), and a 30-minute recovery period at room temperature. Subjects lay supinely in protective covering during the entire experiment. Skin temperatures, oxygen saturation, pulse rates, pulse wave amplitude in the middle finger, and surface electromyography (EMG) activity of the major pectoral muscle were recorded continuously during the test. Before and immediately after the cold exposure, tympanic membrane temperatures were measured. In addition, subjects were asked to estimate cold using a standard scale. RESULTS: During the cold exposure, the decrease in tympanic membrane temperature was not significant.The pulse wave amplitude in the finger decreased sharply upon entering the cold chamber. Skin temperatures, especially of the fingers and toes, decreased during the cold exposure. There were no clear signs of shivering in electromyographic recordings. Subjective cold feelings followed decreasing skin temperatures. Skin temperatures did not return quickly. Even 30 minutes after the exposure, all the skin temperatures still had not returned to normal levels. However, subjective cold feeling was relieved immediately. CONCLUSIONS: Cold exposure provoked immediate protective vasoconstriction in the peripheral compartment, which caused linear decreases of local skin temperatures. This probably was triggered from the unprotected face and upper respiratory areas.     

应用中度低温含氧血停跳液持续灌注心肌保护法的临床疗效分析

应用中度低温含氧血停跳波持续灌注心肌保护方法对20例各种先天性及风湿性心脏病人进行手术治疗，与低温冷晶体停跳液间断灌注方法相比较，此方法临床上表现开放主动脉后心脏自动复跳车高，脱机顺利，术后低心排综合症发生率低，血流动力学稳定，无手术死亡，表明具有较好的心肌保护效果。     

Role of the nitric oxide pathway in kappa-opioid-induced hypothermia in rats

The effect of central and peripheral administration of a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the hypothermia induced by the selective kappa-opioid receptor agonist trans-(+/-)3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide methane sulfate (U50,488H) was studied in male Sprague-Dawley rats. In the first series of experiments, we examined the effect of subcutaneous (s.c.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME, at a dose of 50 mg/kg s.c., had no influence on body temperature (Tb). Coadministration of L-NAME (50 mg/kg, s.c.) with U50,488H (10 mg/kg, s.c.) blocked the hypothermia induced by U50,488H. In the second series of experiments, we investigated the effect of intracerebroventricular (i.c.v.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME itself, given i.c.v. at a dose of 1 mg/rat, did not evoke any change in Tb. Administration of L-NAME (1 mg/rat, i.c.v.) caused a significant suppression of U50,488H hypothermia. The results indicate that either central or peripheral nitric oxide synthesis is required for the production of hypothermia induced by U50,488H.     

Whole blood for the acutely haemorrhaging civilian trauma patient: a novel idea or rediscovery?

The concept of whole blood (WB) as a treatment modality for trauma patients requiring transfusion therapy is not new. Successfully employed in the early 20 century, WB was the product of choice for military trauma resuscitation until the advent of component therapy changed the landscape of transfusion medicine. However, the recognition of the success of WB in the military operational setting has provided some enthusiasm to explore its revival as a cold‐stored option in the civilian trauma resuscitation sector. Concerns continue to exist over potential limitations for its application in regards to the efficacy of platelets after cold storage, the risk of haemolytic transfusion reactions following the transfusion of un‐cross‐matched WB and the logistical issues for civilian blood banks in providing WB. This review aims to reconcile these concerns with data available in the literature, with a view to establishing that there is in vitro evidence supporting the haemostatic effects of cold‐stored WB as a potential therapeutic option in both the pre‐hospital and in‐hospital civilian trauma resuscitation settings.     

Novel applications of therapeutic hypothermia: report of three cases

Therapeutic hypothermia can provide neuroprotection in various situations where global or focal neurological injury has occurred. Hypothermia has been shown to be effective in a large number of animal experiments. In clinical trials, hypothermia has been used in patients with postanoxic injury following cardiopulmonary resuscitation, in traumatic brain injury with high intracranial pressure, in the perioperative setting during various surgical procedures and for various other indications. There is thus evidence that hypothermia can be effective in various situations of neurological injury, although a number of questions remain unanswered. We describe three patients with unusual causes of neurological injury, whose clinical situation was in fundamental aspects analogous to conditions where hypothermia has been shown to be effective.