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Three Part Question

In [newborn infants] is [CRT] an [accurate marker of organ blood flow]?

Clinical Scenario

While working for the neonatal transport team you are involved in the transfer of an extremely low birthweight preterm baby, 28 weeks' gestation, birth weight 800 g, on day 1 of life. The baby is ventilated with stable gases, minimal ventilator requirements and is not receiving any cardiovascular support. On clinical assessment you are concerned as the central capillary refill time (CRT) is prolonged at 4 seconds, despite normal cuff blood pressure. You wonder about the validity of prolonged CRT as a marker of poor organ blood flow in preterm newborns.

Search Strategy

PubMed search with search terms (capillary refill time or capillary refilling time) and neonate revealed 31 papers.

Review of Turning Research into Practice database and BestBETS revealed an evidence-based synopsis assessing the validity of CRT in paediatric intensive care, but no similar review for neonatal practice.


On further review of abstracts 23 were excluded (2 review articles, 2 case reports, 8 not assessing CRT, 9 assessing CRT in non-neonatal age group, 2 comparing CRT with mortality) and 1 was unfortunately unavailable.

Search Outcome

The remaining seven studies are summarised below.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Strozik et al, 1997,	469 Healthy neonates, 28–42 weeks' gestation, single unit, normal observations for preceding 24 h. CRT.5—s pressure, in sternum, forehead, hand and heel	2b, Prospective cohort study with poor follow-up	CRT Mean (SD, 95th centile)	Head = 1.73 s (0.37 s, 2.26 s). Chest = 1.9 s (0.38, 2.65 s) Hand = Non-normal distribution. Foot = Non-normal distribution	Ambient temperature controlled. No significant interobserver variability. No long-term follow-up (to ensure healthy sample)
Strozik et al, 1998	280 Healthy term newborns, single unit, normal observations for preceding 24 h. CRT measured on day 2 or 3. CRT—hand, head and chest Divided into seven groups, with seven different CRT pressure times (1–7 s) Different patient set from Stozik, 1997.	2b, Prospective cohort study with poor follow-up	CRT: Mean (SD, 95th centile)	Head (3 s) = 1.76 s (0.31 s, 2.37 s) Head (7 s) 1.88 s (0.39 s, 2.52 s) Chest (3 s) 1.76 s (0.32 s, 2.39 s) Chest (7 s) 1.82 s (0.35 s, 2.51 s) Hand No significant difference between 3 and 7 s pressure times Non-normal, widely scattered distribution	No significant interobserver variability. No long-term follow-up of sample
Raju et al, 1999	137 Normal newborn term infants, single unit (45, <24 h; 47, 24–48 h;45, 48–72 h). CRT—5 s pressure, in hand and foot. Triplicate measurements. Ambient and skin temperature measured	2b, Prospective cohort study with poor follow-up	Triplicate measurement. Mean (SD, 95th centile)	Temperature. 4.23 s (1.47 s, 7.11 s) CRT: 4.64 s (1.41 s, 7.4 s) Hand Decreasing CRT with each subsequent assessment Foot Inverse relation between CRT and temperature	No long-term follow-up of sample. Only peripheral CRT measured
LeFlore et al, 2005	42 Healthy, term infants, single unit. CRT measured 1–4 h after birth, compared with non-invasive BP and heart rate (gold standards). CRT—fi nger, heel, chest. Pressure 1–2 s (brief) and 3–4 s	4, Poor reference standard	CRT: Mean (SD, 95th centile)	Brief pressure (chest). 2.4 s (0.6 s, 3.58 s) Extended pressure 3.8 s (0.8 s, 5.37 s) No signifi cant correlation with heart rate and CRT. Direct relation with BP and CRT	No long-term follow-up of sample. Non-relevant gold standards (BP and heart rate) in healthy infants. No mention of blinding
Wodey et al, 1998	100 Infants, single unit CRT compared to cardiac index as gold standard CRT—average of hands and feet, 5 s pressure	4, Poor reference standard	Peripheral CRT	Signifi cantly correlated with cardiac index	No definition of abnormal cardiac index (as gold standard). No reference for validity of gold standard. No clear mention of CRT values
Osborn et al, 2004,	128 Infants, <30 weeks’ gestation, two units CRT, invasive BP and CPTd measured and compared to SVC fl ow (gold standard), at 3 h, 5–10 h and 24 h’ CRT—5 s pressure, chest and hand	2b, Exploratory cohort study with good reference standard	Chest CRT.	Correlation between chest CRT and low SVC flow. Area under ROC 0.72 (95% CI 0.64 to 0.80). ≤3 s: LR for low SVC fl ow 2.75. ≤4 s: LR for low SVC fl ow 7.25	Gold standard validated. Appropriate spectrum of patients. Gold standard applied regardless of CRT result. No mention of blinding
Miletin et al, 2009	38 VLBW infants, single unit. CRT, BP, serum lactate and UO measured and compared to SVC flow (gold standard), in first 24 h (median 18 h). CRT measured at head, chest and foot. Pressure applied for 5 s	2b, Exploratory cohort study with good reference standard	CRT (chest, head), UO, BP. Lactate, CRT (foot)	Poor positive correlation with SVC flow. Poor negative correlation with SVC flow.	Gold standard same as CRT measured by staff blinded to other parameters. 50% Of low SVC flow group on inotropes at time of assessment

Comment(s)

Studies (Srozik, 1997, 1998, Raju, LeFlore) measured CRT to determine normal values. Strozik et al (1998) demonstrated a normal distribution of values when assessing central CRT, with values in normal infants below 3 s. Using a similar method to assess CRT, however, LeFlore et al found longer CRT values with a wider normal range. This study is limited by its smaller sample size than (Strozik, 1997, 1998) and because a single observer made all CRT measurements. These studies suggest that central CRT in normal, healthy neonates has a range of up to 4 s. Raju et al attempted to define normal values for peripheral CRT in healthy newborns. The wide variation they found in healthy newborns (up to 10 s), fits with the widely scattered peripheral CRT values obtained by Strozik et al, and suggest that measuring peripheral CRT is of limited usefulness. No studies assessing normal CRT values followed up the samples in the short term to ensure there were no conditions (such as congenital heart disease) that might have affected the CRT values obtained; however, these conditions are sufficiently rare in infants with normal observations, and the samples are large enough, that these studies should still give a good determination of normal values.

Editor Comment

BP, blood pressure; CPTd, core periphery temperature difference; CRT, capillary refi ll time, LR, likelihood ratio; ROC, receiver operating characteristic curve; SVC, superior vena cava, UO, urine output; VLBW, very low birth weight (<1500 g).

Clinical Bottom Line

Central capillary refill time (CRT) seems to have a wide range of normal values (up to 4 s) in newborn infants (grade B).

Peripheral CRT is not a useful assessment of haemodynamic status in neonates (grade B).

Central CRT values ≥4 s may represent significantly reduced organ blood flow (likelihood ratio 7.25 in <30-week gestation infants) (grade B).

References

1. Strozik KS, Pieper CH, Roller J. Capillary refilling time in newborn babies: normal values. Arch Dis Child Fetal Neonatal Ed 1997;76:F193–6.
2. Strozik KS, Pieper CH, Cools F. Capillary refilling time in newborns – optimal pressing time, sites of testing and normal values. Acta Paediatr 1998;87:310–12.
3. Raju NV, Maisels MJ, Kring E, et al. Capillary refill time in the hands and feet of normal newborn infants. Clin Pediatr (Phila) 1999;38:139.
4. LeFlore JL, Engle WD. Capillary refill time is an unreliable indicator of cardiovascular status in term neonates. Adv Neonatal Care 2005;5:147–54.
5. Wodey E, Pladys P, Bétrémieux P, et al. Capillary refilling time and hemodynamics in neonates: a Doppler echocardiographic evaluation. Crit Care Med 1998;26:1437–40.
6. Osborn DA, Evans N, Kluckow M. Clinical detection of low upper body blood flow in very premature infants using blood pressure, capillary refill time, and central-peripheral temperature difference. Arch Dis Child Fetal Neonatal Ed 2004;89:F168–73.
7. Evans N, Kluckow M. Early determinants of right and left ventricular output in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed 1996;74:F88–94.
8. Hunt RW, Evans N, Rieger I, et al. Low superior vena cava flow and neurodevelopment at 3 years in very preterm infants. J Pediatr 2004;145:588–92.
9. Miletin J, Pichova K, Dempsey EM. Bedside detection of low systemic flow in the very low birth weight infant on day 1 of life. Eur J Pediatr 2009;168:809–13.
10. Osborn DA, Evans N, Kluckow M. Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants. Pediatrics 2003;112:33–9
11. Straus SE, Richardson WS, Glasziou P, et al. Evidence-based medicine; how to practice and teach EBM. Edinburgh: Elsevier 2005.
12. Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed 2000;82:F188–94.