Factors that influence the behavioral pain responses of premature infants

Pain, 59 (1994) 101-109 0 1994 Elsevier Science B.V. All rights reserved 0304-3959/94/$07.00

101

PAIN 2.581

Factors that influence the behavioral pain responses of premature infants BonnieJ. Stevens a,*, C. Ceteste Johnston

b and Linda Horton

’

a University of

Toronto, Perinatal Nursing Research, Mount Sinai Hospital, Toronto, Ontario (Canada), ‘McGill University, Montreal Children’s Hospital, Montreal, Quebec (Canada), and ‘Royal Victoria Hospital, Montreal, Quebec (Canada)

(Received 1 December 1993, revision received 2 February 1994, accepted 17 February 1994)

Summary The responses of preterm neonates to acute tissue-damaging stimuli have been described. However, factors which influence these responses have received little attention. In this study, we observed 124 premature infants before, during and after a routine heel lance and determined how two contextual variables (severity of illness and behavioral state) influenced their behavioral responses. Significant changes in facial actions occurred between baseline and the most invasive phase of the heel lance procedure, stick. The fundamental frequency, harmonic structure and peak spectral energy of the infant’s cry were also significantly increased during the stick phase. Behavioral state was found to influence the facial action variables and severity of iilness modified the acoustic cry variables. Accurate identification of pain in premature infants requires consideration of factors that influence their response. Key words: Infant; Preterm; Pain; Behavioral response; Behavioral state; Severity of illness

Introduction The physiologica and behavioral pain responses of premature infants have recently been described in detail. Physiologic responses to tissue-damaging stimuli indicate global distress but are not specific to pain (McIntosh et al. 1993; Stevens and Johnston, in press). Behavioral responses are more consistent and specific to pain in infants of all age groups (Grunau and Craig 1987; Craig and Grunau 1993; Craig et al. 1993; Johnston et al. 1993). Factors which influence behavioral responses have received only minima1 consideration and deserve attention. Systematic investigations of behavioral pain responses in premature infants have included facial actions (Stevens and Johnston 1991; Craig et al. 1993; Johnston et al 1993; Stevens et al. 19931, cry characteristics (Michelsson 1971; Michelsson et al. 1982; Thoden

* Corresponding author:

Bonnie J. Stevens, 50 St. George Street, Toronto, Ontario MSS lA1, Canada. Tel.: (416) 978-2837; Fax. (416) 978-8222.

ssix

0304-3959(94)00057-L

et al. 1985; Johnston et al. 1993; Stevens et al. 1993) and body movements and posture (Craig et al. 19931. Facial reaction to tissue insuh has been characterized by brow bulge, eyes squeezed shut, deepening of the naso-labial furrow, open lips, mouth stretched vertically and horizontally and a taut tongue. This pattern has been reported in studies of adults (Craig et al. 1992), healthy full-term infants (Grunau and Craig 1987) and premature infants (Stevens and Johnston 1991; Craig et aI. 1993; Johnston et al. 1993; Stevens et al. 1993) undergoing acute tissue-damaging procedures. Infants as young as 25 weeks gestation have demonstrated this facial expression, although younger gestational age was associated with less reactivity to heel lance (Craig et al. 1993). The latency, duration and acoustic parameters fundamental frequency, intensi~, jitter, tenseness and mean spectral energy) of the premature infant’s cry have been examined in response to acute pain (Michelsson et al. 1982; Thoden et al. 1985; Stevens and Johnston 1991; Johnston et al. 1993; Stevens et al. 1993). The pain cries of the smallest premature infants were shorter in duration and more high-pitched and harsh than the full-term infants.

102

Body activity during routine heel lance has also been assessed in premature neonates (Fitzgerald et al. 1989; Craig et al. 1993). Craig et al. (1993) devised the Infant Body Coding System (IBCS) to compare body movements of full-term and preterm infants following a painful event. Full-term infants exhibited higher levels of body activity than the preterm infants. All infants showed the most body activity to the most invasive phase (lance) of the heel lance procedure. In Gate Control Theory, Melzack and Wall (1965, 1988) hypothesized that response to a painful stimulus would vary with the context in which it was experienced. To date, little knowledge exists on how contextual factors modify the behavioral pain responses of premature infants. Behavioral state or state organization was derived from general systems theory (Bertalanffy 1968). Wolff (1966, 1987) defined behavioral states as clusters of spontaneous self-organizing behaviors that are more commonly referred to as sleep/ waking states. Smooth transition of the infant from one state to another is thought to reflect the infant’s capacity for integrating environmental input (Emde and Robinson 1980; Prechtl and O’Brien 1982; Wolff 1987). In full-term infants, behavioral state is well organized and transition from one state to another proceeds with ease. The speed and smoothness of changes in state are reflected in the full-term infant’s ability to organize responses in order to interact with the environment (Als et al. 1979). Conversely, the behavioral states of premature infants are less organized and state transitions occur with less facility (Gorski et al. 1979). This diminished organization results in a decreased ability to orient to environmental stimuli and a greater proportion of time spent in the sleep states. It has been hypothesized that the infant’s response to a pain-producing stimulus would be mediated by the context in which it was experienced instead of only reflecting tissue insult. Behavioral state has been shown to act as a mediator of behavioural pain responses in both full-term (Grunau and Craig 1987) and premature (Fitzgerald et al. 1989) infants. Both studies indicated

TABLE

that infants in the alert awake state exhibited the most behavioral activity. The infant’s severity of illness has also influenced the metabolic responses of premature infants experiencing post-operative pain (Anand and Carr 1989; Durand et al. 1989; Anand et al. 1992) and the cries of infants undergoing painful procedures. Michelsson and colleagues (Lind et al. 1970; Michelsson 1971; Michelsson et al. 1977) have reported that premature and sick infants exhibited shorter cry durations and higher fundamental frequencies than full-term infants following noxious stimuli. From these studies, it could be hypothesized that both gestational age and severity of illness may modulate acoustic features of the cry. Previous studies of sex differences in pain-related behaviour of neonates have yielded inconsistent findings. Bell and Costa1 (1964) and Bell et al. (1971) reported that female neonates showed greater behavioural reaction than males to an air jet to the abdomen. Lipsitt and Levy (1959) also found that female infants demonstrated a greater reaction to electrotactual stimulation. Conversely, Grunau and Craig (1987) found that infant males showed shorter latency time to cry and to display facial action following heel lance. Other investigators (Gullickson and Crowell 1964; Owens and Todt 1984) found no sex differences to painful stimulation. Lester and Zeskind (1978) found that lower ponderal index scores (weight by length index) and shorter gestation were associated with cries of shorter duration, a higher fundamental frequency and decreased harmonics. The purpose of this study was to describe the premature infant’s behavioural responses to an acute painful event and to determine how the infant’s behavioral state, severity of illness, gestational age, sex and weight influenced these responses. Method Subjects Infants from the premature nursery of one metropolitan university teaching hospital who were between 32 and 34 weeks (224-238

I

DESCRIPTION

OF INFANT

ATTRIBUTES

Variable

Gestational age at birth (days) Days of life Weight at birth (gl Apgar score (5 mitt) Invasive procedures (frequency) Non-invasive procedures (frequency) Physiological stability index score

(continuous

variables)

Descriptive

statistics

Mean

SD

Min

Max

230.6 3.3 1037.3 8.2 11.6 21.2 4.3

6.32 I.5 390.6 I.1 6. 1 17.4 4.7

222 I Ill0 5

244 5 2920 IO

I

33

0 0

73 19

103 TABLE II FREQUENCY

OF INFANT ATTRIBUTES

Variable

(categorical variables)

Frequency of occurrence Freauencv

% Total

Sex

Male Female Type of delivery Spontaneous vaginal Vaginal with epidural Cesarian section (G/A) Cesarian section (epidural) Infant diagnosis Prematurity (Prem) Prem + hyperbilirubinemia Prem + RDS (mild) Prem + apnea Prem + RDS (moderate-severe) Prem + RDS + hyperbilirubinemia Prem + infection Prem + intrauterine growth Retardation Prem + necrotizing enterocolitis Type of medication No medications Antibiotics (Ant) Ant + bicarbonate Ant + calcium gluconate Ant + caffeine Other

blood was collected in micropipettes or test tubes. This protocol was divided into 4 phases including baseline (60 set), warming (60 see), stick (15 set) and squeezing (30 set).

67 57

54 46

22 42 25 34

17.7 33.9 20.2 28.2

34 43 13 11 8 5 4 4

27.4 34.7 10.5 8.8 6.5 4.0 3.2 3.2

2

1.6

16 57 17 17 11 8

12.9 46.0 13.7 13.7 8.9 4.8

days) postconceptual age, less than or equal to 5 days of life, free of major congenital anomalies or neurological abnormalities and not requiring a respirator or surgery were eligible to participate in the study. Infants who were not singletons or twins, had received analgesics or sedatives 48 h prior to data collection or had greater than grade 1 intra-ventricular hemorrhage (IVH) were ineligible. Of 138 eligible infants, parents of 124 consented to have their infants participate. Characteristics of these infants are reported in Stevens and Johnston (in press) and summarized in Tables I and II.

Measures Behavioral outcomes included facial activity and cry. Body activity was not evaluated as the premature infants were often restrained by equipment. Facial activity was assessed using the Neonatal Facial Coding System (NFCS) (Grunau and Craig 1987, 1990). Facial actions included brow bulge, eye squeeze, naso-labial furrow, open lips, stretch mouth (vertical and horizontal), lip purse, taut tongue, chin quiver and tongue protrusion. Inter-rater and intra-rater reliability was established utilizing faces fTOm 30 infants selected at random. Inter-rater reliability was established with 2 independent raters and calculated using Cohen’s kappa. Inter-rater reliability for all variables averaged 0.88. Intra-rater reliability was assessed by the testretest procedure (having the same rater score the facial actions of the same 30 infants 2 weeks apart). Intra-rater reliability averaged 0.90. Cry characteristics were measured using computerized spectrographic analysis. They included fundamental frequency (F,) (Hz), harmonic structure (% disphonated or blurred), peak spectral energy (Hz), cry duration (% of time) and latency to cry (set). Inter-rater and intra-rater reliability were established using the same statistical procedures as for the faces and averaged 0.89 and 0.90, respectively. Grunau and Craig’s (1987, p. 3981 adaptation of Prechtl’s (1974) observational rating system was used to assess behavioral state during the 60 set prior to baseline. Infants were classified as being in quiet sleep, active sleep, quiet awake or active awake. Inter-rater agreement of 89% was obtained. The neonatal Physiologic Stability Index (PSI) (Georgieff et al. 1989) was used to assess severity of illness. During the previous 24 h, each physiological variable on the PSI was assigned a score reflecting the degree of abnormality or the clinical importance of the derangements. The original PSI (Yeh et al. 1984) was developed and validated for critically ill children that excluded premature infants. Georgieff et al. (1989) modified the PSI to reflect neonatal physiology in premature infants. The psychometric properties (criterion and construct validity) of the instrument were estalished by correlating the neonatal PSI scores with the Therapeutic Intervention Scoring System (Keene and Cullen 1983) and a nursing utilization intetvention system (Georgieff et al. 1989). Gestational age (days), weight (g) and sex of the infant plus other extraneous variables were collected from the infant’s medical record following data collection.

Apparatus Facial activity was videotaped on a Panasonic 2510 VCR (with real-time counter) and cries were audiotaped on a Sony TCM 5000 with Senneheiser MKE 2.3 microphone through all phases of a routine heelstick procedure. Phases of the heelstick procedure were signalled simultaneously on the audiotape and the audio channel of the video recording with a 1000 Hz tone generated manually by the investigator. Tones were generated by a shure mixer which was inaudible during the data collection procedure.

Procedure Informed consent was obtained from the parent by the research nurse. Testing was conducted at the infant’s cot or isolette in the premature nursery when routine blood was required to determine the health status of the infant. The heel lance was performed by one research nurse for all infants in the study in the morning between IO:00 and 12:OOh, at least 1 h following the infant’s feeding. The standard protocol for sampling blood involved warming the foot in a small cup of warm water, picking up and rubbing the foot with alcohol to disinfect the skin, incising the heel with a small disposable metal scalpel (4.9 mm long) and squeezing the heel until sufficient

Coding and reduction

ofdata

The raw facial and cry data were subjected to coding and/or data reduction. A video cassette recorder with remote control, stop action and slow motion feedback and a 48 cm playback colour monitor were used by trained coders for the second-to-second analysis of the facial activity. The frequency and percent occurrence of the 10 facial actions were examined across the phases of the heelstick procedure. Tongue protrusion, chin quiver and lip purse were virtually absent (less than 1%) in the study infants’ responses and were eliminated from the analyses. The audiotape of the heelstick procedure was reviewed to determine the tatency to cry from heelstick and cry duration for each phase for each infant. The first two expiratory cries in the stick and squeeze phase of the procedure were then transformed by Fast Fourier Transform (FFT) for spectrographic analysis (O’Shaughnessy 1987; Johnston and O’Shaughnessy 1988). Only two cries from each phase were analyzed, as earlier work by Johnston and Strada (1986) has shown that the greatest changes in acoustical parameters of the cry occur during the initial cries. Only those infants who cried for both the stick and squeeze phases of the heel lance procedure were

104 included in the analyses. The software program utilized for cry analysis was C-SPEECH (Milkenovic 1990). Missing data for the dependent variables were estimated from the previous or subsequent data collection period (3 set) as long as only a minimal amount (i.e., less than 5%) of data were missing. This occurred as a result of equipment, procedural or mechanical failure. If more than a minimal amount of data were missing, the case was eliminated from data analysis for the particular response concerned. Approximately 5% of cases were eliminated for missing data.

Results

Means, range and variance of the independent and dependent variables were calculated. Assessment of behavioral state indicated that the majority (approximately 80%) of premature infants were in one of the sleep states prior to the heelstick procedure. The mean PSI score for the sample was 4.3 (SD = 4.7; range: O-18). The PSI raw scores were reduced to 4 categorical groups (healthy, mildly ill, moderately ill, severely

TABLE FACIAL Variable

III ACTION

VARIABLES Behavioural

BY BEHAVIOURAL

STATE

ACROSS

PHASES

OF THE HEELSTICK

PROCEDURE

state Awake

Sleep

Baseline BB ES NLF OL VMS HMS TT Warming BB ES NLF OL VMS HMS TT Stick BB ES NLF OL VMS HMS TT Squeeze BB ES NLF OL VMS HMS TT

ill) and compared to the independently calculated raw PSI scores by 3 neonatal experts. (The reduction process is described in detail in Stevens and Johnston, in press.) A kappa of 0.86 was calculated. Repeated-measures multivariate analysis (RM MANOVA with 1 repeated measure; phase) was then used to determine how variables changed as a group over the phases of the heelstick procedure. To determine the influence of behavioral state and severity of illness, RM MANOVA was performed with PSI group and behavioral state as the between-subjects factors. This is an appropriate analysis as each subject has multiple continuous variables measured at multiple times. As well, the subjects could be divided into between-subject discrete categorical grouping factors. Repeated-measures multivariate analysis of covariance (RM MANOCOVA) was utilized to control for the constant effects of gestational age, sex and weight. Changes in the proportion of individual facial actions at each phase of the heelstick procedure are

SD

Active Mean

SD

(2.3) (36.1) (0.0) (5.4) (3.2)

1 1 47 0 0 0

(1.5) (1.7) (2.7) (44.1) (0.0) (0.0) (0.0)

24 19 29 75 6 0 1

(5.8) (9.7) (9.1) (30) (14) (0.0) (2.6)

13 8 II

(22.9) (17.1) (16.7)

12 12 16

(26.0) (26.4) (25.8)

62 56 6S

34

I I

(37.4) (0.4) (2.3) (1.0)

2 1

(40.0) (2.4) (6.7) (3.2)

50 2 7 0

(41.0) (5.6) (24.4) (0.0)

87 9 8 Y

(38) (43) (30) (22) (20) (20) (18)

64 55 63 70 5 29 13

(30.5) (33.1) (33.5) (30.1) (10.1) (32.3) (22.8)

71 57 63 7s 15 34 18

(29.1) (33.5) (30.4) (30.3) (24.9) (34.20 (26.7)

76 75 67 81 17 28 24

(28.1) (28.3) (32.3) (27.6) (26.0) (29.6) (30.5)

Yl 74 Y2 9.5 32 54 44

(16) (32) (11) (IO) (31) (29) (40)

51 41 51 56 7 22 7

(41.6) (41.1) (41.9) (38.8) (20.1) (33.9) (16.1)

69 50 59 67 11 29 21

(34.8) (37.3) (37.1) (36.7) (21.7) (39.2) (30.8)

70 61 69 84 18 37 23

(31.8) (35.5) (31.4) (24.3) (27.6) (37.1) (27.2)

72 59 68 85 19 37 31

(37) (42) (40) (25) (27) (36) (38)

Active Mean

Quiet Mean

SD

1 0 0 16 0 1 0

(6.2) (0.0) (0.0) (35.1) (0.0) (4.6) (0.0)

6 28 0 1 1

7 4 Y

(20.9) (3.9) (20.7)

24 0

SD

3

(8.6)

I

c-2.1)

1

Quiet Mean

I

105

Fig. 1. Proportion

of the

squeeze

Stick

WarIll Phase

Heelstick

of individual

Procedure

facial actions

by phase.

displayed in Fig. 1. There was a significant multivariate main effect of phase (F (21,103) = 19.3510, P < 0.0001) with the greatest differences existing between baseline and stick and baseline and squeeze. All 7 facial actions contributed to this multivariate effect. There was also a significant multivariate main effect of phase (F (3, 52) = 4.3074, ~0.002) with the cry characteristics. Maximum fundamental frequency, peak spectral energy, and harmonic structure were significantly higher during the stick than the squeeze phase of the heelstick procedure. There was no significant difference in cry duration between the 2 phases. The mean values and standard deviations for each facial action by PSI group and behavioral state across the phases of the heelstick procedure were calculated for the RM MANOVA. There was no significant multivariate interaction effect of behavioral state by PSI group (F (21, 332) = 1.0002, P < 0.477) with the facial action outcomes and no significant multivariate main effect of PSI group (F (56, 763) = 1.0002, P < 0.477) with the facial actions.

TABLE

There was, however, a significant multivariate main effect of behavioral state (F (21, 31.5) = 3.3340, P < 0.0001) on the facial action variables. There was also a significant multivariate interaction effect of behavioral state by phase (F (63, 2478) = 2.4933, P < 0.0001). This interaction suggests that there was a variable impact for the manner that behavioral state modulated facial activity at each phase of the heelstick procedure and across phases. Individual facial actions that contributed most to the 2-way interaction effect included brow bulge (F (9, 356) = 3.8031, P < O.OOOl),eye squeeze (p (9, 356) = 6.4171, P < 0.0001) and nasolabial furrow (F (9,356) = 5.1632, P < 0.0001). Infants in the quiet sleep state had fewer increases in the proportion of facial actions than infants in active sleep. The proportion of time (calculated as a percentage of total time) that each facial action (by behavioral state) was present during each of the 4 phases of the heelstick procedure is summarized in Table III. Simple effects were employed to further delineate how (a) the facial actions of infants in the various behavioral states changed at each phase and (b) infants in each behavioral state changed across phases. There were significant multivariate differences in facial actions between infants in the 4 behavioral states at baseline (F (21, 344) = 6.2546, P < O.OOOl),warming F (21, 344) = 3.6054, P < O.OOOl>,and stick F (21, 3444)= 1.7294, P < 0.025). At baseline and warming, infants in the active sleep state exhibited significantly more facial action than infants in any other behavioral state on all variables except horizontal mouth stretch and taut tongue. At stick, infants in the active awake state had significantly more vertical mouth stretch and taut tongue. There were no significant multivariate differences at heelsqueeze phase of the heelstick procedure (F (21, 344) = 1.1617, P < 0.283). The facial actions of infants in each state also

IV

CRY VARIABLES Variable

BY PSI GROUP

AT THE

STICK AND SQUEEZE

PHASES

OF THE HEELSTICK

PROCEDURE

PSI group Healthy

Ill

Mean

SD

Mildly Mean

SD

Moderatety Mean

SD

Severely Mean

SD

751 1768 22 75 1.2

(453) (665) (19) (23) (2.4)

1003 1854 23 70 1.5

(526) (704) (23) (25) (2.8)

1097 2358 31 50 1.8

(566) (606) (22) (29) (2.3)

1321 2437 34 38 2.8

(841) (691) (27) (31) (3.5)

556 1778 18 70

(182) (613) (24) (22)

670 1396 18 68

(393) (224) (23) (24)

737 1797 16 55

(341) (615) (18) (31)

1138 2201 19 30

(677) (820) (23) (31)

Stick MaxFo (Hz) PkSE (Hz) Harm (%) Dur (%> Lat (set) Squeeze MaxFo PkSE Harm Dur

changed significantly across the 4 phases of the heelstick procedure. Infants in the active sleep state and the quiet awake state had significant increases in all facial actions across the 4 phases. Infants in the quiet sleep state had fewer significant increases in the proportion of facial actions than infants in active sleep. In particular, there was no significant increase in taut tongue at stick or vertical mouth stretch at squeeze. Infants in the active awake state had fewer significant facial action changes than any other group, particularly at the squeeze phase of the procedure where there was no significant increase in any facial action. There was no multivariate interaction effect of behavioral state by PSI group (F (28, 176) = 0.6327, P < 0.937) and no main effect of behavioral state (F (12, 129) = 0.52994, P < 0.892) with the cry variables. There was, however, a significant multivariate main effect of PSI group (F (12, 129) = 2.4132, P < 0.009) with the cry variables. Severely ill infants had a higher peak fundamental frequency, higher peak spectral energy and shorter cry duration than healthy and mildly ill infants. The cry characteristic by PSI group at the stick and squeeze phases of the heelstick procedure are summarized in Table IV. When the effects of weight and gestational age at data collection were controlled (RM MANOCOVA), there were no multivariate main effects of PSI group (F (21, 336) = 1.0843, P < 0.363) or sex (t; (7, 114) = 1.0322, P < 0.395) on the facial action responses. Consistent with the results of the RM MANOVA, there was a multivariate main effect of behavioral state (F (21, 336) = 3.1979, P < 0.0001). All facial actions except horizontal mouth stretch contributed to the multivariate effect. When weight and gestational age at data collection were controlled, there were no significant multivariate main effect of behavioral state (F (12, 153) = 0.5573, P < 0.873) or sex (F (5, 109) = 1.1723, P < 0.660) with the cry variables. Consistent with the RM MANOVA analysis, there was a significant multivariate main effect of PSI group (F (12, 153) = 2.0020, P < 0.027).

Discussion Significant changes in behavior occurred at the most invasive phases of the painful event in preterm infants of 32-34 weeks gestation. Factors influencing these changes were different for facial actions and cries, indicating that different external factors must be taken into consideration when assessing the complex nociceptive response. Not all changes in the behavioral responses occurred exclusively during the most stressful phases of the heelstick procedure. Although many of the behavioral responses assist in clarifying the premature infant’s reaction to a tissue-damaging stimulus,

they do not guarantee correct identification individual infants.

of pain in

Facial expression

Brow bulge, eye squeeze, nasolabial furrow and open lips, which were most prevalent and significantly associated with healthy full-term newborns (Grunau and Craig 1987) and preterm infants (Craig et al. 1993; Johnston et al, 1993) following noxious stimulation, were also most significantly increased following heelstick in the present study. Tongue protrusion, chin quiver and pursed lips, which were not frequently associated with tissue-damaging stimuli in full-term and preterm infants were also virtually absent in this study during the heelstick procedure. Vertical and horizontal mouth stretch and taut tongue were less increased in the most painful phases of the procedure as compared to non-painful phases. Vertical mouth stretch and taut tongue were almost absent (< 1%) in the baseline and warming phases of the heelstick procedure in this study suggesting that these facial actions were reasonably specific to the most painful events. However, there was no adequate comparison of the infant’s response to tissue-damaging versus non-tissuedamaging stimulus in this study. In order to determine which facial actions (individual or in combination) are most specific to tissue-damaging stimuli, a study examining the infant’s responses to both tissue-damaging and non-tissue-damaging stimuli under identical conditions would need to be undertaken. Facial activity has been the most consistent response to tissue-damaging stimuli across studies and different infant, child and adult populations. Yet, as Craig and his colleagues (1993) suggest, there is a need for age specific norms in order to best interpret the significance of behavioral response to noxious events. The present study, which described the presence (or absence) and magnitude of behavioral responses of a large group of premature infants to a tissue-damaging stimulus could be considered a beginning in establishing these norms. The findings in the present study are consistent with the results of Craig et al. (1993) and Johnston et al. (1993). The same facial actions were present in premature infants (in similar proportions at heelstick) but to a lesser extent than in full-term infants. Both groups of investigators determined that younger gestational age was associated with a less vigorous response pattern. In contrast, there was no significant effect of gestational age in the present study. This result is most likely due homogeneity of the study sample, in that all infants were between 32 and 34 weeks gestation.

The comparison of pain and non-pain cries was beyond the scope of this study as very small percent-

107

ages of infants cried during the baseline (2%) or warming (9%) phases. Rather, the intent was to describe the acoustical features of cries in response to a tissuedamaging stimulus. Thus, only cry characteristics of those infants who cried for both the stick and squeeze phases (62%) were analyzed. Cry characteristics of premature infants in this study were consistent with those described as ‘pain’ cries in other research on both premature and full-term infants. Increases in peak fundamental frequency, peak spectral energy and total cry duration were the most commonly reported features. These features fit the cry characteristics that adult listeners perceive as aversive and urgent (Zeskind and Lester 1978). Fuller (1991) suggests that these characteristics may form the basis for adult differentiation of pain versus other types of cries. Infants cry to signal distress. However, similar to facial expression, crying is not unique to pain. Acoustical analyses of specific features of the ‘pain’ cry in full-term neonates have provided researchers with graded information regarding the intensity of the distress (Porter et al. 1988; Zeskind and Marshall 1988; Fuller 1991; Benini et al. 1993) but little categorical information regarding the source of an infant’s distress. The absence of crying cannot be interpreted as an absence of pain. The reasons why infants do not cry in response to painful procedures are not well understood by researchers in this area. Behavioral state and severity of illness

Behavioral state was easily identifiable in infants of 32-34 weeks gestational age. However, the organization of behavioral states and the speed and ease with which they moved from one state to another may not have been comparable with full-term infants. This may be reflected in the greater proportions of time these premature infants spent in non-alert waking and sleep states. Grunau and Craig (1987) have demonstrated that facial activity in response to a noxious stimulus in full-term neonates was found to be a function of behavioral state prior to the noxious event, rather than solely reflecting tissue damage. Behavioral state prior to the heelstick procedure in the present study also had a significant effect on the premature infant’s facial expressions during the heelstick. Infants in both sleep states had significant increases in the proportion of facial actions across the 4 phases with the largest increase at heelstick. Infants in quiet sleep had smaller changes in facial actions than those in active sleep, particularly in the mouth actions. Heelstick produced the most dramatic change in facial action in infants in all behavioral states except active awake. Infants in the active awake state had greater proportions of all facial actions than any other group during

the baseline and warming phases of the heelstick procedure. These differences are not surprising given that the definition of active awake state involves facial action. Facial activity may be a less discriminating response in infants in the active awake state. At the stick phase, there were significant differences in infants in the sleep states versus the awake states in vertical mouth stretch and taut tongue. Infants in both awake states had significantly greater proportions of both facial actions than infants in the sleep states. At heelsqueeze, the only significant difference was in the greater proportion of taut tongue in infants in active awake (as compared to those in quiet sleep). Vertical mouth stretch and taut tongue, which appear to be discriminating features of pain, are also modulated by behavioral state. There was no effect of behavioral state on the temporal or acoustical properties of the cry in this study. There were no significant differences in facial actions according to severity of illness. However, there was a non-significant decrease in the proportion of time that each facial action was present with increasing severity of illness. This trend suggests that sicker infants are capable of expressing their pain through facial actions, although the ability to sustain this response may be weak. Contrary to the effect of severity of illness on facial activity, there was a significant effect of severity of illness on cry. The peak fundamental frequency, peak spectral energy, cry duration and latency to cry accounted for this multivariate effect. Severely ill infants had significantly higher peak fundamental frequency, shorter cry duration and longer latency to cry than healthy and mildly ill infants at the stick phase. These results are consistent with Lester and Zeskind’s (1982) biopsychosocial explanation of infant crying where cry characteristics are thought to reflect the infant’s biological integrity or an index of underlying stress. Lester suggests that due to neurological disorganization, sicker infants produce cries that are higher pitched, tense, grating and generally more attention demanding than healthy infants. This phenomenon has been noted in premature infants (Michelsson 1971; Michelsson et al. 1983) and full-term infants with certain chromosomal aberrations (Vuorenkoski et al. 19661, neurological abnormalities (Michelsson et al. 1977; Michelsson et al. 1984), hyperbilirubinemia (Wasz-Hockert et al. 1971) and birth asphyxia (Michelsson 1971). The effect of severity of illness on the cry outcomes needs to be interpreted with caution as the analysis included only those infants who cried for both the stick and squeeze phase of the heelstick procedure (68% of infants cried for the stick only, 73% of infants cried for the squeeze only and 62% cried for both stick and squeeze). This missing data creates both statistical and measurement dilemmas. However, in examining the

total sample, there were no significant differences in clinically significant variables including apgar score at 5 minutes, frequency of invasive (tissue-damaging) and non-invasive (non-tissue damaging but potentially painful) procedures, severity of illness and behavioral state between those infants who cried and those who did not. There was a trend in the data (P < 0.06) for a greater proportion of those infants in the awake state to cry at one or both invasive phases of the heelstick procedure than those infants in the sleep states. Future secondary analysis of this data will include the development of regression models to determine how crying or not crying adds to the explanation of variance in other dependent variables such as the significant facial actions. When the co-variates of sex, weight and gestational age were controlled, there were no significant interaction effects on the facial action or cry responses. Similar to when these co-variates were not accounted for, there was a significant effect of behavioral state with the facial action variables and a significant effect of severity of illness with the cry characteristics. The 3 co-variates did not influence the behavioral responses of the infant to a tissue-damaging stimulus. These results are consistent with Brackbill and Shroder’s (1980) position that there is not strong evidence for behavioral differences between full-term male and female infants. However, the findings are not consistent with Grunau and Craig’s (1987) study where sex differences in speed of response (boys showed shorter latency to cry and facial action following heel lance) were reported. Until such time that a clear body of evidence either supporting or refuting the importance of this factor emerges, sex differences need to be considered as a factor which may modulate pain responses. This study has provided support for a profile of infant behavioural responses to a tissue-damaging stimulus that can be modulated by factors such as behavioral state and severity of illness. This profile will lead to the development of a measure for improved assessment of the infant’s response to presumably painful or noxious procedures. Better assessment of the infant’s responses to these stimuli will produce better management of pain and decreased risk to the infant’s Integrity and health.

thank Dr. Robert Usher, Linda Horton, R.N., the nurses and staff of the premature nursery at the Royal Victoria Hospital in Montreal, Canada and the families of the infants who participated in the study. Financial support from Health and Welfare Canada (No. 66063861-471, the Medical Research Council of Canada, the Canadian Nurses Foundation, the Hospital for Sick Children Foundation, Toronto, Ontario, The Pharmaceutical Manufacturers of Canada and the Faculty of Graduate Studies and Research, McGill University is acknowledged.

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