nursing chronotherapeutics: a conceptual framework

Nursing Chronotherapeutics: A Conceptual Framework Una E. Westfall

Nurses frequently make decisions about when treatments and actions are performed. The nursing concern driving this review is the timing of nursing activities to optimize desired and minimize untoward effects. A nursing conceptual framework is proposed that highlights individual and environmental factors, as they relate to rhythmic responses, as well as places within the framework for nursing actions based on customary and usual temporal patterns.

[Keywords: clinical decision making; conceptslconstructs related to health]

t

herapeutics are assisting measures taken with, or on behalf of, patients and significant others to manage and reduce effects of illness and to improve and promote health and health-related behaviors (Clinical Therapeu- T tics Task Force, 1988). Nursing therapeutics are assist-

ing measures for which nurses have decision and action respon- sibilities. Determining the time for an activity often is a nursing responsibility because nurses frequently sequence, implement or ensure that actions are carried out. Thus, temporal placement or timing- of measures can be viewed as a nursing therapeutic.

This paper proposes a conceptual framework for timing as a nursing clinical therapeutic by: 1) clarifying characteristics of rhythms; 2) exploring timing as a clinical therapeutic; and 3) proposing a nursing chronotherapeutic conceptual framework.

Rhythms

Predictable temporal patterns are ubiquitous, as exemplified by the passage of days, the ebb and flow of tides, and the changing seasons of the year. A rhythm is "a sequence of events ... that repeats (itself) through time in the same order and at the same interval" (Minors & Waterhouse, 1981, p. 321). When a rhythm originates within an organism, it is said to be endogenous or self- initiated.

* *

Peak Time Peak

~-

Figure 1 : Schematic of rhythmic characteristics.

Rhythms have common characteristics depicted in Figure 1. They can span different periods or time intervals. A common period is close to but not exactly 24 hours. Such rhythms of -24

Una E. Westfall, RN, PhD, Beta Psi, i s Assistant Professor, School of Nursing, Oregon Health Sciences University. The author thanks Linda Felver, RN, PhD and Susan Woods, RN, PhD for their contributions to the early development of ideas expressed here. Correspondence to Department of Adult Health and Illness Nursing, L-456, School of Nursing, Oregon Health SciencesUniversity, 3181 SWSamJackson ParkRoad, Portland,OR97201- 3098.

Accepted for publication January 15, 1992.

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Nursing Chronotherapeutics: A Conceptual Framework

hours (24+4) are called circadian (circa-about, &is-day); when less than 20 hours, ultradian; when longer than28 hours, infradian. Infradian rhythms may include such time frames as multiple days (e.g., a week), a month or a year.

In addition to period length, single rhythms display features of amplitude (magnitude of peak to trough [nadir] difference), peak time (when the crest or maximum value occurs, usually given in clock hours or a reference point such as midsleep, or hours after light on); level or mean (average or midpoint value of the period) and waveform (graphic composite of peak time, period, slope of ascending and descending curves, and amplitude that depicts progression from any given point to the next point characterized by the same phase).

The rhythmic quality of “phase” can be used to describe temporal relationships among two or more rhythms (Minor & Waterhouse, 198 1). There may be reference to rhythms being “in phase” with one another. Internal synchronization of rhythms by the body’s timekeeping system is the usual condition. An example of such a relationship is that of circadian rhythms of rest (sleep)-activity and growth hormone in adults. Normally, growth hormone plasma levels rise sharply and peak early in the sleep portion of the sleep-activity cycle. When there is time displace- ment of one rhythm, there can be transient desynchronization among other rhythms. Some rhythms are able to adjust to environmental cues more quickly than others. For example, when rest-activity, temperature and urinary excretion of sodiumrhythms were compared in humans following a time shift, rest-activity adjusted more quickly then temperature, and temperature more quickly than urinary sodium excretion (Wever, 1979). When subjects experienced a six hour phase-advance (comparable to traveling west to east across six time zones), partial entrainment with environmental cues took -3 days for rest-activity rhythm; -4 days, temperature; and -7 days, urinary sodium excretion. More detailed presentations of rhythmic phenomena are available (Arendt, Minors & Waterhouse, 1989; Minors & Waterhouse, 1981; Moore-Ede, Sulzman & Fuller, 1982).

Clinical Therapeutic: Timing

Timing focuses on the question of when an action will provide its optimal benefit or cause the least harmful impact. Living organisms are not homostatic, i.e., the same or constant. If physiology varies predictably over a time period, then the individual can be said to be biologically different at different times within the period (Folk, 1974; Halberg, et al, 1973; Moore- Ede et al., 1982). Reactions may be anticipated to be different when the same stimuli are introduced at different times of the day. Much temporal pattern research has been conducted with animals (especially rodents), in part to control for environmental stimuli and to gain access to tissues. Halberg and co-workers (as reported in Reinberg, 1967) exposed rodents to various noxious agents, including E. coli and ouabain. When the same amount of each agent was given at different times during a 24-hour period, mortality rates differed dramatically. These rates ranged from <10 percent to >70 percent with E. coli exposure (<lo percent when given during late activity hours) and 15 percent to 75 percent for ouabain (15 percent when given during early activity

phase). The only difference was in the clock hour, or time, of exposure.

In a study with five healthy males, Moore-Ede, Meguid, Fitzpatrick, Boyden & Ball (1978) infused the same dose of intravenous potassium at noon and at midnight. The plasma potassium concentration was found to be 40 percent higher following the midnight dose than after the noon dose. More recently, in patients with constant heparin infusion rates, activated partial thromboplastin and thrombin time values differed by as much as -50 percent and 60 percent respectively between specimens drawn at night and in the morning (Decousus et al., 1985). The role that rhythms play in health and disease has yet to be clearly determined; however, there is evidence to support the view that there are times within biological rhythmic cycles when an individual’s vulnerability and resistance fluctuate (Hrushesky, 1983; Reinberg, 1967).

Conceptual Framework: Nursing Chronotherapeutic Model

To examine timing as a nursing therapeutic, a proposed nursing chronotherapeutic model has been adapted from work by Heitkemper and Shaver (1989) and presented in Figure 2.

Nur,infi.2rlt(inito: 0 * Alter c ti<%

EndogenousRhydrms fxiemalhv. Intemalbv. Sensory Receptorb) lnternd Pacernaker(s) Light: Dark Neural Pathways Food Availability Periodic:Predidive Age Time (Eating: Fasting) Other Biologic Rhythms aronotvpe K q i n g Social Ecology *Rangeoffrequencies

SVStem Temperature 4mmdary 1 Aperiodic: Readbe

Atmospheric Responses tostimuli Pressure Geomagnetic Field

Individual Responses: I Overt Rhythm(s)

phvsioloai RhVthmK Behavioral Experiential dh hms Y

a *Resistance * Susceptibilty

Figure 2: Proposed Nursing Chronotherapeutic Model

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In this model, individual factors and environmental cues lead to individual responses, some of which are overt rhythms. It is these rhythmic responses that are phenomena of nursing concern (ANA, 1980), and are categorized as physiologic, pathologic, behavioral, and experiential. Within the framework proposed, places are highlighted for the nursing therapeutic of timing. Nursing actions can be linked to selected environmental cues and to overt rhythmic responses, and less directly to individual factors.

Individual Factors Individual factors are endogenous to the organism and in this

model include rhythms, sensory receptors, internal pacemakers (time clocks), neural pathways, age and chronotype.

Endogenous Rhythms: An endogenous rhythm, or the endogenous component of an overt rhythm (sometimes referred to as periodicity), exists independent of environmental factors, but can be synchronized by an internal time-keeping system. The endogenous component ensures that under constant environmental conditions, period-predictable fluctuations continue. When a self-generated and self-maintained rhythmic period is not iden- tical to that of environmental cues (e.g., 24 hours), the rhythm is said to be free-running. These rhythms, however, can be influenced by the environment.

Sensory Receptor: Sensory receptor integrity and intact affer- ent pathways are necessary for environmental input. Some receptors with their accessory structures can be adjusted to enhance or decrease input. Ways in which this can be done include adding or removing eye glasses and patches, removing or replacing hearing aids and cleansing the mouth of any coating interfering with taste buds.

Internal Pacemakerfs): Considerable research have been directed toward identifying and tracing the body’s internal time- keeping system. The best documented location of one (not the only) time-keeping center is the suprachiasmatic nuclei (SCN), paired clusters of cell bodies located in the anterior hypothala- mus, just distal to the optic chiasm. Disruption of locomotion, rest-activity, sleep (particularly slow wave type), drinking and feeding rhythms have been reported following bilateral SCN destruction (Czeisler, Richardson, Zimmerman, Moore-Ede & Weitzman, 1981; Hobson & Steriade, 1986; Krieger, 1980; Moore-Ede et al., 1982; Nishio, Shiosaka, Nagakawa, Sukumoto & Satch, 1979; Rodieck, 1979).

It is posited that projections or neurotransmitter substances from the SCN, or both, act as timing messengers to distant receptor sites active in various endogenous rhythms. Such cen- ters and communication links are proposed as part of the timekeeping system. Researchers are now exploring components of this system.

Age: A review of changes in aging noted differences in some rhythms (Casale & deNicola, 1984). In an older population, rhythms amplitudes often were decreased, and period length, shorter or more labile.

Chronotype: This word refers to the characteristic of morningness-eveningness-type (Kerkhof, 1985). Other terms used include “early birds” and “night owls.” Horne and Ostberg (1976, 1977) generated a tool to measure an individual’s

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propensity toward being a “morning-” or “evening-” type. Temporal pattern differences have been reported for measured rhythms such as temperature, activity, and salivary cortisol values, with “morning-type’’ individuals manifesting earlier peak levels than persons rating themselves as “evening-type.’’ Such findings support chronotype as a factor in periodicity.

Environmental Cues Multiple environmental fluctuations exist external to the indi-

vidual. In this proposed model, environmental cues also may be external to the body’s time-keeping system but part of the individual’s internal environment.

Recall that endogenous rhythms can be influenced, but are not generated, by the environment. When an environmental cue “captures” the endogenous rhythm period length ( e g , from -24 to exactly 24 hours), the cue is called a zeitgeber (zeit-time, geber-giver), a synchronizer, or an entraining agent (Aschoff, Fatranska Giedke, Coerr, Stamm & Wisser, 1971; Halberg & Lee, 1974; Reinberg & Smolensky, 1983). These roughly equiva- lent terms refer both to initiating and maintaining a coalescing between environmental cues and corresponding endogenous rhythms. Because of environmental richness, few experimental human studies have successfully tested for a single environmental cue; however, exploration of environmental links with endogenous rhythms have been pursued with animals.

External Environmental Fluctuations Studied environmental aspects include such recurring events

as light-dark (light-dusk-dark-dawn) (Czeisler et al., 198 1 ; Czeisler et al., 1989; Moore-Ede et al., 1982; Reinberg & Smolensky, 1983; Wilkinson, Shinsako & Dallman, 1979), noise-quiet (Moore- Ede et al., 1982; Reinberg & Smolensky, 1983; Wever, 1979), food availability-nonavailability (Moore-Ede et al., 1982; Moore- Ede, 1986; Stevenson, Day & Sitren, 1979; Stevenson, Sitren & Furuya, 1980) as well as temperature (Moore-Ede et al., 1982; Reinberg & Smolensky, 1983) atmospheric pressure (Moore- Ede et al., 1982), electromagnetic field differences (Wever, 1970) and social interactions (Aschoff et al., 1971; Halberg, Halberg, Barnum & Bittner, 1959; Wever, 1979), including activity and rest (sleep) phases.

Lighting cycles have been acknowledged as strong zeitgebers for animals and more recently, humans (Czeisler et al., 1989). In a thoughtful critique, Czeisler and colleagues (1981) raised issues about lighting cycles as a zeitgeber for humans. Subse- quently, in research with humans using a set lighting cycle and otherwise constant conditions (Czeisler et al., 1981), or bright light exposure (Czeisler et al., 1989) multiple rhythms including body temperature, bedrest-activity, and urine output were synchronized with lighting changes.

Both food and fluid (water) availability have been proposed as zeitgebers. Findings from animal studies do not support the simple presence of fluid as a zeitgeber for rhythms tested (Moore- Ede et al., 1982). There is, however, general agreement that restricted food availability can be a powerful zeitgeber (Scheving, 1976) for multiple rhythms in animals (Nelson, Scheving & Halberg, 1975; Phillippens, Von Mayersbach & Scheving, 1977; Sulzman, Fuller & Moore-Ede, 1977). Corresponding results

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with humans have yet to be determined, although with more accessibility to food, one may posit considerably less influence of this cue on human rhythms.

“Daily routine” or schedule (social ecology) is often cited as a powerful synchronizer for humans derived from early work by Halberg et al. (1959). The reported daily routine encompassed multiple sensory stimuli, including light, sound and temperature fluctuations, as well as social interactions. Wever (1979) also reported social cues as strong human zeitgebers. In his study, however, light fluctuations were coupled with the presence (or absence ) of a gong sound. Subjects were observed responding to the sound but not to the lighting change. The gong was interpreted as a link to the researcher, and thus a “social” cue. An alternative explanation for the response is that it was the sound itseg with or without a link to a person.

Stronger support for social ecology as a human zeitgeber may be found in rhythmic studies where groups were isolated. One such study was with seven women isolated in a cave “living as a group” for 14 days (Reinberg, 1971). Inside the cave, there were two tents; three women in one, and four in the other. Two separate temperature rhythms were found among the seven subjects. Women in one tent had a significantly different temperature peak time than the women in the second tent.

Other environmental fluctuations that have been explored, at least to a limited degree, include temperature (Moore-Ede et al., 1982), sound (Wever, 1979), atmospheric pressure and geomagnetic fields (Wever, 1970, 1979). Results to date support the position that if these elements do exert a synchronizing effect, it is modest at best. Species-specific responses may also enter the picture.

Methodological problems have plagued several studies seek- ing to characterize temporal patterns, necessitating cautious interpretation of reported findings. Such problems include statis- tical analysis methods used, sample sizes, species differences and a “constant environment.” To determine which particular zeitgebers, alone or in combinations, can entrain specific human rhythms, precise separation and testing would be needed. To date environmental cues have been isolated, adjusted, and maintained mainly in laboratories and with multiple animal species. Separate human testing of many of these cues, including geomagnetic fields and atmospheric pressure-pose unique chal- lenges. Coalescing of rhythms with selected environmental cues has been reported, although the evidence with humans is vari- able.

Internal Environmental Conditions In the model, additional environmental cues are posited to

exist within the individual, but outside the time-keeping system. Gender has been included as an internal environmental condi-

tion because of hormonal differences. Wever (1984) measured sleep-wake and temperature rhythms in 33 subjects (12 female and 21 male) and found measurable differences in the sleep- wake rhythm by gender, with women demonstrating shorter intrinsic sleep-wake rhythms than men. However no differences were found in intrinsic temperature rhythms.

Folk (1974) and later Moore-Ede (1986) proposed that biological rhythms serve an adaptive purpose. Such rhythms act as

corrective responses to cyclic environmental changes. This anticipatory response has been called predictive, or periodic, homeostasis. Such homeostasis contrasts with responses to aperiodic environmental input, termed reactive homeostasis (Moore-Ede, 1986).

Predictive responses: Multiple rhythms with temporal relationships exist within an individual. Wilkinson (1989) proposed that several physiological oscillatory factors influence biological rhythms. Rhythmic fluctuations in properties such as levels of substances, responsiveness, or receptor concentration could contribute to enhancing or minimizing the ability to react. One of many examples can be found in the adrenal cortex. The adrenal gland has been found to vary in its responsiveness to plasma ACTH levels during the course of a day (Dallman, Akana, Cascio, Darlington, Jacobson & Levin, 1987; Dallman, Engeland, Rose, Wilkinson, Shinsako & Siedenburg, 1978).

Reactive responses: Reactive responses occur following environmental changes and encompass a wide range of mechanisms activated to attain or maintain viable equilibrium (Moore-Ede, 1986). It is possible that reactive responses may “mask” a smaller, basal endogenous rhythm. Whether or not the endogenous rhythm continues to oscillate during the time of reactive response is only now being explored.

Environmental Influences

Individual factors and environmental cues have been presented separately; however, the two merge through a time- keeping system, leading to individual responses manifested by measurable overt rhythms. Within their range of entrainment, rhythms can be modified by environmental cues. Findings from animal studies support the position that different rhythms have different ranges of entrainment and points beyond which rhythms do not remain coupled to environmental cues (Moore-Ede et al., 1982). In one set of experiments, activity rhythms remained synchronized with light-dark phases until the period length dropped to 20 hours. Then, activity rhythms began to free-run.

In contrast to endogenous rhythms, environmental cyclic fluctuations may produce responses that are predictable, but not self-initiated. An example of such responses is the postprandial increases in plasma glucose and insulin levels following food intake. If food is ingested on a regular schedule, the marked plasma glucose and insulin values rise on a regular basis; however, when food is withheld, there is loss of this regularity and amplitude in plasma glucose and insulin levels. Interest- ingly, plasma insulin levels have been found to have an endogenous rhythmic component (Bellinger, Mendel, & Moberg, 1975; Goodner et al., 1977). The greater influence from an exogenous caloric load, however, can obscure or overshadow this endogenous rhythm.

Individual Responses of Overt Rhythms Measured rhythmic responses may be categorized as physi-

ological, such as those found for blood glucocorticoids and insulin levels, heart rate, liver glycogen content and core body temperature; pathologic, such as jet lag, seasonal affective disorder, and phase shifting as well as tumor cell metabolism;

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behavioral, such as performance speed, error occurrence and oral behavior (smoking, eating, drinking actions); or experiential, such as hunger, mood, pain intensity and perception of time passage. Although endogenous rhythms in each of these catego- ries exist, such rhythms can be modified by exogenous environmental influences.

Nursing Actions

A person’s customary and current rhythms supply a base for nursing actions. Such actions are directed toward environmental stimuli and overt rhythmic responses. Additionally, nurses assess individual factors.

Nurses can manipulate the environment, such as lighting cycles, to provide or strengthen zeitgebers consistent with an individual’s customary environment. Actions can also be taken to decrease extraneous environmental stimuli, especially input likely to interfere with usual zeitgebers. In addition, the nurse can act to decrease and prepare for aperiodic environmental stimuli. These measures can include such activities as closing or opening doors, reducing interruptions, controlling delays in scheduled care, and providing anticipatory sensory teaching about procedures and tests (Johnson, 1972; Johnson, Kirchhoff, & Endress, 1978). With this framework, there is the added perspective of when during a day such information and events would have maximal benefit.

Nursing therapeutic measures also direct planning actions based on knowledge of the individual’s customary and present rhythms. Though data gathering may not be a clinical therapeutic per se, it provides information that can be used in modifying interventions to coincide with known customary and present rhythms. Assessment of rhythms may offer useful direction about individual periods of susceptibility or resistance in relation to prescribed treatments and activities. It is the adjustment of activities to match more closely the person’s rhythms that is the clinical therapeutic of interest here. From a nursing perspective, such adjustments would be directed toward establishing baseline fluctuations, maximizing times of resistance, and protecting the individual during times of susceptibility.

Nurses are responsible for assessing individual factors iden- tified in the framework. Such data gathering can enhance the nursing therapeutic of timing. For example, not knowing about the integrity of sensory systems, or if persons consider themselves to be “morning-”or “evening-” type people, can interfere with individualizing nursing actions. Likewise, assessing customary environmental routines provides the basis for tak- ing action based on specialized knowledge of the individual.

In summary, this nursing chronotherapeutic model gives direction for nursing actions based on customary and current rhythms of the individual. Through such nursing activities, the concept of predictive homeostasis can be operationalized by selecting the time of actions to match or coincide with an already prepared response pattern. While much remains to be learned, it is clear that nurses are in a unique position to observe and enhance temporal patterns when caring for patients. @&

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nursing chronotherapeutics: a conceptual framework

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