Results
After removal of duplicates, our search identified 527 studies, of which 309 were excluded after abstract and title review (figure 1). Of 214 full text articles screened by two reviewers, 21 were included in the current review. Of the included papers, 15 described studies carried out in high-income countries (as determined by the World Bank), with the remaining 6 describing studies carried out in middle-income or low-income countries. Full details of individual study characteristics are given in Table 1.
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Figure 1.
Flow chart for papers identified by search strategy. CRT, capillary refill time.
Quality assessment of included studies is summarised in figure 2, with full details in web appendix 3 http://adc.bmj.com/content/100/3/239/suppl/DC1. Quality was generally good; all studies measured CRT on all included children and all comparators were judged to be objective. The lowest quality scores were found in the two criteria related to blinding. This was generally poorly reported, but sometimes impossible to implement, e.g. when investigating the effect of site of measurement or pressing time.
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Figure 2.
Bar chart showing quality assessment of included papers. Four papers with detail on normal ranges only are excluded from assessments of some quality criteria. CRT, capillary refill time.
Relationship Between CRT and Other Measures of Cardiovascular Status
Each of the four included studies (111 children) investigated different measures, and was small (maximum 42 subjects). In healthy children, decreased arterial blood flow in the lower limb induced by inflation of a tourniquet was associated with increased CRT of just under 1 s for a 10-fold decrease in arterial blood flow. A study of healthy neonates found no clear correlation between CRT and blood pressure.
Two studies investigated correlations between CRT and measurements of cardiovascular status using cardiac catheters in intensive care settings. The children mostly had acute infections, such as septic shock and pneumonia. One study found positive predictive values of 93%–96% and negative predictive values of 40%–50%, depending on the site used for CRT measurement, for CRT >2 s to predict low superior vena cava oxygenation (≤70%). The second found significant correlations between CRT and both core-peripheral temperature gap (r=0.66, p<0.0001) and stroke volume index (r=−0.46, p=0.001), although no significant correlation was seen with cardiac index or systemic vascular resistance index. The same study noted a weak correlation (r=0.34, p=0.02) between CRT and central venous pressure.
Normal Ranges of CRT
Seven of the 13 studies (n=1252) reporting normal ranges were conducted in 953 newborn infants up to 7 days of age. We present data on normal ranges in newborn infants and older children separately, organised by body site, as three studies in children of both age groups found clinically relevant differences in CRT measured at different sites.
Figure 3 shows a forest plot of the upper limit of the normal range for newborn infants up to 7 days of age, measured at six sites: the head, chest, abdomen, hand, finger and foot. Significant statistical heterogeneity was not explained by clinical factors and was present at all sites, so summary results are not reported. Upper limits of the normal range of CRT in newborns ranged from 2.5 s to over 7 s. The largest range of values was seen at the foot, but upper limits of over 5 s were also found at the finger, hand and chest.
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Figure 3.
Forest plot of upper limits of capillary refill time (CRT) in normal infants (≤7 days of age). Data from the 3–4 s pressing time in the LeFlore and Engle22 study were included in the meta-analysis, as this corresponded more closely to the pressing times reported by other included studies, which were typically 3 or 5 s. *Excluded from meta-analysis as multiple measurements were made on the same participants.
Data on the upper limit of the normal range of CRT for older children (1 week–18 years) (figure 4) was available from three sites: the chest, finger and foot. In most of the included studies, the anatomic site was pressed for 5 s. The summary upper limit for CRT measured at the foot was 4.05 s (95% CI 3.61 to 4.49 s). Unexplained significant heterogeneity (I>75%) was present in data from both the chest and finger, precluding summary estimates. However, all the 95% CI for the upper limit at the chest were below 4 s. At the finger, the maximum upper limit for CRT was 2.08 s; all the 95% CI for the upper limits were below 2.5 s.
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Figure 4.
Forest plot of capillary refill time (CRT) in normal infants and children 7 days to 18 years of age. ^Excluded from meta-analysis as paper reported median and 95th percentile (shown), rather than mean and SD. *Excluded from meta-analysis as multiple measurements were made on the same participants.
Three studies, all on normal newborn infants, reported the distribution of CRT values measured at different sites. Two reported that measurements made at the head and chest approximated a normal distribution, those at the hand appeared less normal and those at the foot were more widely scattered. However, the third study reported a normal distribution for measurements made at the hand and foot.
Four studies assessing the difference in normal range with age were identified, of which three investigated only infants in the first week of life. The fourth was limited by small sample size (n=8 in each age group) and did not report consistent results at different body sites.
Effect of Confounding Factors on CRT Values
Effect of Body Site. Eight studies (n=691) investigated the relation between measurement site and CRT (Table 2). Most assessed healthy children or infants, and were comparable in terms of pressing time and measurement method (e.g. stopwatch), although the amount of pressure used and the number of observers varied.
Included studies assessed CRT at eight body sites: forehead, sternum/chest, hand, finger, lower abdomen, thigh, heel and sole/foot (figure 5). All but one study found statistically significant differences, with clinically significant differences (>1 s) between mean CRT at different sites in three studies. Measurements on the lower extremities were typically longer than those on the upper extremities, head or chest.
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Figure 5.
Visualisation of comparisons between capillary refill time at different sites. Thin lines indicate a single comparison between two sites. Multiple comparisons are indicated with thicker lines labelled with the number of comparisons.
Effect of Pressing Time. Pressing time was examined in two studies of 322 healthy term infants (figure 6). One study compared pressing times of 1–2 s and 3–4 s at the finger, chest and heel on 42 infants, and found CRT significantly increased by 1.2–1.4 s with longer pressing times. The second study also found significantly longer CRT for most of the longer pressing times at the head and chest, but differences were small (0.17–0.42 s) and inconsistent (see web appendix 4 http://adc.bmj.com/content/100/3/239/suppl/DC1). Pressing times did not influence CRT at the heel.
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Figure 6.
Forest plot of differences in capillary refill time (CRT) with various pressing times in healthy infants (≤7 days of age). ^Strozik et al27 compared seven pressing times (1, 2, 3, 4, 5, 6 and 7 s), at each of three sites (head, chest and heel), as well as composite data for pressing times of 3–7 s for the head and chest. Comparisons were not pairwise, as each pressing time was tested on 40 independent infants, therefore, we selected the following clinically relevant pairs for comparison: 7 vs 1 s, 3 vs 1 s, 4 vs 2 s, 5 vs 2 s, 5 vs 3 s, and, where possible, 3–7 vs 1 s.
Effect of Ambient, Skin and Core Temperatures. Four studies on 558 children investigated the effects of ambient, skin and core temperatures. Two provided data on the effect of ambient temperature on CRT in 292 neonates and another on 32 older children (see web appendix 5 http://adc.bmj.com/content/100/3/239/suppl/DC1). Studies varied in the room temperatures compared, body sites and population characteristics, precluding meta-analysis. Two reported significant inverse correlations between ambient temperatures and CRT, with a 5°C decrease in ambient temperature resulting in >1 s increase in CRT in one study. Conversely, a third study found a significant positive correlation, at ambient temperatures of 26°C–30°C.
Two studies assessing the relationship between CRT and skin temperature at the measurement site also found inverse correlations. A further two studies compared the effect of core temperature on CRT. One found a statistically significant relationship, although a decrease of 2°C–3°C in core temperature would be required for a 1 s increase in CRT. The second study found no significant difference in CRT between febrile (core temperature >38.3°C) and afebrile children.
Reliability of CRT Measurement
We found limited evidence regarding reliability of CRT measurements. Seven studies examined interobserver reliability on 485 children (web appendix 6 http://adc.bmj.com/content/100/3/239/suppl/DC1), but results were highly variable, with reliability ranging from poor (κ<0.15) to good (κ=0.54 and 0.65). Using stopwatches to measure CRT appeared to be associated with better interobserver reliability.
There was even less data on intraobserver reliability. One small study in 32 children found strong agreement (ICC=0.96) between three repeated measures and a second study in 20 children showed that CRT decreased with successive measurements at the same site (p<0.0001).