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Neonatal blood gas sampling methods

Anu Goenka, BSc, MB ChB, DFSRH, DTM&H, MRCGP, MRCPCH

Roopesh Bhoola, MB ChB FCPaed (SA), Cert Neonatol (SA)

Neil McKerrow, BA, MB ChB, DCH(SA), FCPaed (SA), MMed (Paed), PG Dip Int Res Eth

Department of Paediatrics, Pietermaritzburg Metropolitan Hospitals Complex

Corresponding author: A Goenka (anugoenka@hotmail.com)

Blood gas sampling is part of everyday practice in the care of babies admitted to the neonatal intensive care unit, particularly for those receiving respiratory support. There is little published guidance that systematically evaluates the different methods of neonatal blood gas sampling, where each method has its individual benefits and risks. This review critically surveys the available evidence to generate a comparison between arterial and capillary blood gas sampling, focusing on their relative accuracy and complications, as well as briefly mentioning the management of such complications. This evidence-based summary and guidance should help inform best practice in the neonatal intensive care unit, and minimise the exposure of babies to unnecessary and potentially serious risk.

The most accurate and non-invasive method of measuring oxygenation is oxygen saturation monitoring. Indwelling arterial catheters are a practical, reliable and accurate method of measuring acid-base parameters, provided they are inserted and maintained with the proper care. Capillary blood gas sampling is accurate, and a good substitute for radial ‘stab’ arterial puncture, avoiding many of the complications of repeated arterial puncture.

You work in a regional neonatal intensive care unit. An 8-day-old premature baby with a right radial arterial catheter develops severe ischaemia of the right hand.

The baby was born at 28 weeks’ gestation with a birth weight of 1 100 g. He had been ventilated since the first few hours of life, initially for severe hyaline membrane disease subsequently complicated by nosocomial pneumonia. A radial arterial catheter was sited on day 6, before which multiple repeated radial ‘stab’ arterial blood gases had been performed.

You immediately remove the radial arterial catheter and begin vasodilatory treatments including warming of the contralateral upper limb, application of 2% nitroglycerin ointment and axillary brachial plexus sympathetic nerve block. However, the ischaemic injury to the right hand does not resolve, and after a further 10 days necessitates amputation of the 3rd, 4th and 5th digits.

You wonder whether anything could have been done to prevent this baby’s peripheral vascular injury, and what the evidence base is with regard to the different methods of neonatal blood gas sampling.

Blood gas sampling and acid-base determination are critical tools in the assessment and monitoring of neonates with respiratory or circulatory compromise, in particular those receiving respiratory support. Blood gas measurement is also part of the basic assessment of most metabolic conditions, including renal, liver and endocrine abnormalities as well as inborn errors of metabolism.

There are various methods for obtaining a blood gas sample from a neonate. This article aims to survey the evidence regarding the accuracy, use and complications of the commonly used methods of neonatal blood gas sampling in order to make best practice recommendations. Brief guidance is also given on the management of complications arising from blood gas sampling. While non-invasive techniques such as transcutaneous blood gas monitoring are discussed in part, the focus is on systematic review of the evidence concerning the relative benefits and harms of invasive methods of blood gas sampling.

Search strategy

Primary sources

Ovid MEDLINE (1948 - 2011) was searched using the following search terms: (blood gas OR blood sampling) AND (capillary OR arterial OR indwelling OR umbilical OR puncture) including related terms. The search was limited to human biology, newborn population and English language. This yielded 252 results, from which 17 studies were selected. Similar additional searches were performed during the review as the relevance of additional topics such as pulse oximetry and transcutaneous blood gas measurement emerged. Further studies were found on examination of the reference lists of the included papers.

Secondary sources

The Cochrane database yielded 3 reviews using the same search criteria as above, and an additional review was found later during a search for reviews concerning neonatal procedural pain.

Which methods of neonatal blood gas
measurement can be used?

Methods of neonatal blood gas measurement include:1

• indwelling arterial catheters, e.g. umbilical or peripheral arterial line (which also allow invasive blood pressure monitoring)

• peripheral arterial ‘stab’ puncture sample

• capillary blood sample (commonly taken from a heelstick)

• non-invasive methods: oxygen saturation monitoring, end-tidal carbon dioxide (CO2) monitoring and transcutaneous oxygen tension­/CO2 monitoring.

Which method gives the most accurate
information?

Acid-base information obtained from blood gas samples taken from an indwelling arterial catheter appears to be the gold standard,1 and is the method by which alternative methods (i.e. capillary blood gas sampling) are compared in the literature. Standard information included in most invasive blood gas measurements consists of pH, partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), bicarbonate (HCO3) and base excess.

Oxygenation (O2)

Invasive blood gas sampling is not the best way to assess oxygenation in a neonate. There is a weak correlation of pO2 between capillary samples and arterial blood taken from indwelling arterial lines.2 However, even pO2 measurement in blood samples taken from indwelling arterial lines only yields single-point pO2 measurement, and does not offer dynamic and continuous information on oxygenation. Oxygenation should be monitored by non-invasive measurement of oxygen saturation (SpO2), which is continuous, reliable, and should be available as the standard of care in all institutions caring for sick newborns.5 Carefully titrated oxygen therapy with the aim of targeting a pre-defined range of oxygen saturations may be important in preventing free radical damage from oxygen toxicity such as retinopathy of prematurity.6 Transcutaneous oxygen tension monitoring (TcPO2) has been suggested as an alternative to SpO2monitoring, but there is insufficient evidence to prove that it is any better in terms of reducing morbidity.7 Other problems associated with TcPO2 monitoring include skin burns, as well as the need for frequent calibration and rotation of monitoring sites.8

Ventilation and acid-base (pH, CO2, HCO3)

A meta-analysis has helped establish the strong correlation of pH, pCO­2 and HCO3 between arterial and capillary blood in adults.9 Courtney et al. have systematically reviewed the neonatal literature published before 1990 concerning the correlation between arterial and capillary blood gas measurements, as well as performing their own study.10 Almost all the studies demonstrated strong correlation between arterial and capillary pH, and HCO3 if measured. Employing a tabular format, the authors describe results of 102 , 3 , 11 of the 14 relevant studies as demonstrating ‘good’, ‘close’ or ‘satisfactory’ correlation between arterial and capillary measurements of pCO2­.

There is variation in the study populations and methodology across the studies included in the review by Courtney et al.,10 making comparisons difficult. Most of these variations are discussed in the review. However, an additional observation is that only 412 , 19 of the studies contain data from preterm infants. Additionally, although most of the studies attempt to induce vasodilatation at the intended site of capillary puncture, their methods vary from different ways of warming the skin2 , 10 , 14 , 17 , 19 , 20 to vasodilatatory creams and iontophoretic techniques.3 , 15 , 16 Capillary and arterial samples were not taken simultaneously in 511 , 17 , 21 out of the 14 studies, which as Courtney et al. note,10 could potentially affect the comparison of arterial and capillary measurements. Potentially painful procedures such as capillary and arterial ‘stab’ puncture blood gas sampling have been shown to cause measurement bias by decreasing oxygenation/ventilation during the procedure itself secondary to crying.22 However, overall it is difficult to quantify how such methodological differences might specifically contribute to differences between the results.

There is also variation in the methods used to express results across the studies, some2 , 11 , 20 quoting the mean difference (with standard error) between paired capillary and arterial measurements for pH and pCO2, while other studies3 , 16 , 17 calculate the correlation coefficient (r). Two of the studies do not employ any numerical or statistical analyses, exclusively presenting their data visually on scatter plots.15 , 19 Courtney et al. identify 4 studies that do not recommend the use of capillary blood gas sampling in neonates on the basis of poor observed power of capillary measurements for predicting arterial pCO2. At least 210 , 20 of these studies (including Courtney et al.’s own) do in fact demonstrate correlation between the arterial and capillary pCO2 measurements, but they are of less clinical value owing to wide scatter limits.

Our literature search did not reveal any additional studies published before 1990 examining arterial and capillary correlation for pCO2 and pH, except for the 14 studies in the comprehensive review by Courtney et al. 10 Since 1990 there have only been 2 comparable studies in the neonatal population, and 3 comparable studies in the paediatric population. Table 1 demonstrates that 4 of these 5 studies published after 1990 show strong correlation between paired capillary and arterial measurements of pCO2. All studies demonstrate good correlation between paired capillary and arterial measurements of pH, and HCO3 if measured.

In summary, systematic review of all the neonatal literature concerning paired capillary and arterial measurements reveals unanimously good correlation for pH, and good correlation in most studies for pCO2. There are difficulties in speculating as to why 3 studies20 , 21 , 23 failed to demonstrate good pCO2 correlation, as these studies do not commonly share any variation in population characteristic or methodology different from the rest of the studies. Our review therefore concludes that capillary blood gas sampling can be used to measure pCO2­ accurately.

Non-invasive CO2 monitoring consists of two techniques: end-tidal CO2 monitoring (ETCO2) and transcutaneous CO2 monitoring (TcPCO2). Molloy et al.27 performed a review of neonatal non-invasive CO2 monitoring, and highlighted that 2 out of the 3 studies they reviewed demonstrated good correlation between ETCO2 and arterial pCO2. They comment, however, that ETCO2 lacks precision, and therefore measurement may be more useful for screening purposes or trending. There are several studies investigating the accuracy of TcPCO2, and after due consideration Molloy et al.’s review concludes that TcCO2 performs better than ETCO2 with regard to correlation with arterial pCO2.27 The general limitations of transcutaneous monitoring highlighted above such as skin burns apply to TcCO2 monitoring.

Other biochemical parameters and pre-analytical considerations

Other biochemical parameters can be measured using capillary blood and show strong correlation with arterial blood, such as haematocrit, haemoglobin, sodium, calcium, glucose, bilirubin and lactate.4 , 28 , 29 Haemolysis from the capillary sampling method is likely to be responsible for the poorer correlation between arterial and capillary blood for potassium and chloride.4 Such haemolysis is more likely in the presence of polycythaemia,30 and should prompt collection of a free-flowing venous or arterial sample. Polycythaemia is also associated with spurious hypoglycaemia, and anaemia can likewise give rise to falsely elevated glucose readings.31

The presence of hypothermia, hyperthermia or increased capillary refill time does not appear to affect the accuracy of capillary blood gas results.26 Indeed, warming the heel before heelstick capillary sampling does not appear to increase accuracy.2 , 32 The presence of hypotension may affect the accuracy of results, which should prompt consideration of arterial sampling.25 Pre-analytical considerations are also important when sampling from indwelling arterial catheters. It has been suggested that for a neonatal indwelling arterial catheter with a dead-space volume of 0.6 ml, at least 1.6 ml of blood should be withdrawn before collection of a blood gas sample to avoid contamination errors from the flush/perfusate.33

What are the complications associated with the various sampling methods?

Invasive blood gas sampling is associated with a wide array of complications. The majority of the neonatal evidence comes from case reports; however, there are some observational studies and even systematic reviews, although these tend to concern prevention or management of complications. The results of our literature search are presented in Table 2, which shows that capillary heelstick sampling is associated with fewer and less serious adverse effects than arterial sampling.

Repeated radial arterial ‘stab’ puncture has been described as ‘difficult, dangerous and unpractical’.13 Table 2 demonstrates there is some evidence for this claim, particularly since capillary sampling is associated with fewer adverse events which can be prevented more easily. In general, the complications associated with indwelling arterial catheters are serious in nature, and arterial catheters should therefore be removed without delay when no longer required.66

Indwelling arterial catheters can be inserted peripherally (radial, posterior tibial or doralis pedis) or centrally in the umbilical artery. Table 2 outlines the evidence behind the recommendation that catheterisation of the brachial and temporal arteries should be avoided. There is also opinion that ulnar artery catheterisation is similarly risky owing to the possibility of ulnar nerve damage or abnormal or compromised collateral blood supply of the hand.56 , 74 It has also been suggested that use of the Allen test in detecting adequate collateral circulation before radial arterial puncture may not be a reliable predictor of subsequent risk of vascular injury.75

Conclusion and recommendations

Indwelling arterial catheters remain a practical, reliable and accurate method of neonatal blood gas sampling, provided they are inserted and maintained with the proper care. Capillary blood gases are accurate and a good substitute for radial ‘stab’ arterial puncture for most babies, avoiding many of the complications of repeated arterial puncture.

Based on our review of the evidence, we propose the following simple guideline for blood gas sampling in neonates:

Proposed neonatal blood gas sampling guideline

1. Reasonable attempts should be taken to site indwelling arterial catheters* (radial, posterior tibial, dorsalis pedis or umbilical – procedure described elsewhere76 ) only if the need for regular blood gas analysis is anticipated.

2. When indwelling arterial catheters are not feasible or not indicated because of infrequent sampling, heelstick capillary blood gases should be the first-line sampling method for acid-base analysis.

3. Peripheral arterial ‘stab’ sampling has little place in neonatology.†

*Caregivers must be informed of the benefits of catheterisation, as well as the common complications such as infection, haemorrhage and vascular injury. Catheters should be inserted in a safe and sterile manner, and removed as early as possible. Heparinised saline should be continuously infused, and no other fluid or medication should ever be given through the catheter. Nursing and medical staff must be vigilant in monitoring extremities to look for signs of vascular compromise.

†Arterial stabs should only be performed under the following circumstances:

• point measurement of pO­2 when oxygen saturation monitoring is unavailable or impossible

• acid-base information required in the clinical scenario of hypotension.

BEST PRACTICE

How to obtain a heelstick capillary blood gas sample

(adapted from Capillary Blood Sampling Guideline, Great Ormond Street Hospital, London, 201077 )

1. Consider procedural analgesia before performing any painful procedure on a neonate. Options include breastfeeding, expressed breastmilk, or administration of 0.5 - 2 ml of 25% sucrose on the tongue 2 minutes before the procedure.78

2. Universal precautions should be observed during this procedure.

3. The baby’s heel should be held with your non-dominant hand, with your fingers around the ankle and lower leg, while partly encircling the baby’s heel with your thumb

4. Select an appropriate site for heelstick puncture:

a. the chosen site should not be extensively traumatised from previous heelstick puncture

b. vascular injury risk is reduced by puncturing the medial or lateral aspects of the heel

c. avoid the posterior and central regions of the heel, as puncture of these sites can cause damage to nerves, tendon, cartilage and bone

d. avoid inflamed/oedematous tissue.

5. Clean the site with an appropriate neonatal antiseptic solution (such as 0.5% chlorhexidine in 70% isopropyl alcohol79 ) and allow to dry.

6. Puncture the skin using an appropriate lancet device (depth 0.85 mm for a premature baby, 1.0 mm for a term baby).

7. Wipe away initial blood flow with cotton wool.

8. Maintain grip while gently compressing the heel to produce a droplet of blood.

9. Collect the droplet of blood using an appropriate capillary tube (pre-heparinised electrolyte-balanced heparin80 ).

10. Release compression while maintaining grip to allow re-perfusion, and then re-compress to allow further formation of further droplets of blood.

11. Repeat until desired sample volume has been obtained.

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57. Prian GW, Wright GB, Rumack CM, O’Meara OP. Apparent cerebral embolization after temporal artery catheterization. J Pediatr 1978;93(1):115-118.

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58. Macnicol MF, Anagnostopoulos J. Arrest of the growth plate after arterial cannulation in infancy. J Bone Joint Surg Br 2000;82(2):172-175.

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65. Johnson FE, Sumner DS, Strandness DE. Extremity necrosis caused by indwelling arterial catheters. Am J Surg 1976;131(3):375-379.

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Table 1. Review of neonatal and paediatric literature post-1990 concerning correlation of paired
capillary and arterial measurements of pH and PCO2

Citation

Study population

Methodology

Results
(correlation between capillary and arterial measurements)

Statistical significance

Saili et al.,23 1992

51 neonates with moderate birth asphyxia of gestational age 32 - 38 weeks, and postnatal age of 48 - 72 hours

Simultaneous paired arterial and capillary samples

Capillary samples obtained after foot warming

pH r=0.92

pCO2 r= 0.32

p<0.05 for both pH and pCO2

Harrison et al.,24 1997

50 PICU patients aged from 1 month to 220 months with various pathologies, 53% of patients ventilated

Simultaneous paired arterial and capillary samples

No extremity warming prior to capillary sampling

pH r 2 =0.903

pCO2 r 2 =0.955

p<0.0001 for both pH and pCO2

Escalante-Kanashiro et al.,25 2000

75 samples from PICU patients from 0.6 - 134 months (including 8 neonates) with various pathologies

Simultaneous paired arterial and capillary samples

Capillary samples obtained after finger warming

pH r=0.87

pCO2 r=0.86 (correlation reduced in the presence of hypotension r=0.52, but not altered by poor perfusion or hypothermia/pyrexia)

No quoted measure of statistical significance

Yang et al.,4 2002

33 premature infants admitted to NICU, birth weight range 635 - 2 500 g

Capillary blood taken 5 minutes after arterial sampling

No extremity warming prior to capillary sampling

pH r=0.92

pCO2 r=0.93

No quoted measure of statistical significance

Yildizdaş et al.,26 2004

116 samples from PICU patients (including 8 neonates) with varying pathologies, 28% of patients ventilated

Simultaneous paired arterial and capillary samples

Capillary blood taken from heel in infants and finger of children

No extremity warming prior to capillary sampling

pH r=0.823

pCO2 r=0.988 (correlation unchanged by poor perfusion, hypotension or hypothermia/pyrexia)

pH p<0.001

pCO2 p<0.001

PICU = paediatric intensive care unit; NICU = neonatal intensive care unit.


Table 2. Review of neonatal literature concerning complications of different methods of blood gas sampling with suggested prevention and management strategies

Adverse event

Procedure

Evidence

Strategies to avoid or treat adverse event

Pain

Capillary heelstick

Arterial puncture

Systematic review34

Breastfeeding or supplemental breastmilk35

Non-nutritive sucking36

Sucrose solution37

Bruising

Calcaneal osteomyelitis

(can result in flatfoot and calcaneal deformity – case reports38 )

Capillary heelstick

Neonatal case reports39 , 40

Use of an automated (spring-loaded) incision device reduces bruising compared with a conventional manual lancet41

Optimal depth of lancet puncture 0.85 mm42

Site of lancet puncture43 (see diagram in ‘How to obtain a heelstick capillary sample’)

Calcified cutaneous heel nodules

Capillary heelstick

Neonatal case report44

None found

Haematoma

Arterial puncture

Neonatal case reports45

Apply direct pressure to site after puncture

Rotate puncture sites46

Pseudo-aneurysm

Arterial puncture

Neonatal case report47

Some suggestion that repeated puncture should be avoided47

Arteriovenous fistula formation

Radial arterial puncture

Neonatal case report48

Some suggestion that repeated puncture should be avoided48

Carpal tunnel syndrome

Radial arterial puncture

Neonatal case report45

None found

Median nerve damage

Brachial arterial puncture

Neonatal case reports49

Avoid brachial artery puncture due to high (13%) incidence of median nerve damage49

Infiltration and extravasation injury

Peripheral arterial catheter

Neonatal case reports50

Management depends on severity, options include: observation alone, impregnated occlusive dressings (e.g. hydrocolloids) or irrigation with 0.9% saline or hyaluronidase51

Haemorrhage

Peripheral arterial catheter

Umbilical arterial catheter

Neonatal case reports52

Use of three-way tap systems for sampling52

Cumulative blood loss from repeated sampling

All sampling methods

Neonatal observational study53

Rational ordering of blood tests54

Blood sample tubes with ideal fill lines54

Retrograde embolisation

Peripheral arterial catheter

Neonatal experimental study55

Use of small volume flushes (0.5 - 1 ml is suggested),56 which are injected slowly

Cerebral embolisation

Temporal arterial catheter

Neonatal case reports57

Avoid temporal arterial catheterisation56

Arrest of growth plate

Peripheral arterial catheter

Neonatal case reports58

None found

Infection (superficial abscess)

Peripheral arterial catheter

Neonatal case reports52

Breadth of topic beyond scope of this review. In brief, helpful measures include:59 strict hand hygiene for all involved in care, strict aseptic technique during insertion of line, minimise unnecessary access ports, regular change of ports/giving sets, sterilise ports before access, removal of line when not necessary

Infection (bacteraemia)

Peripheral arterial catheter

Umbilical arterial catheter

Review article59 (which quotes audits and retrospective studies)

Catheter occlusion and thrombosis

For umbilical arterial catheter also includes:

• aortic thrombosis

• hypertension and haematuria

Umbilical arterial catheter

Peripheral arterial catheter

Systematic review60

Meta-analysis which includes neonatal studies61

Umbilical arterial catheter – continuous infusion of heparinised saline (0.25 - 1 U/ml) reduces thrombotic risk60

Peripheral arterial catheter – continuous infusion of heparinised saline (1 U/ml) reduces thrombotic risk61

For extensive or limb-threatening thrombosis consider thrombolysis with recombinant tissue-type plasminogen activator (rTPA)62


CONTINUED: Table 2. Review of neonatal literature concerning complications of different methods of blood gas sampling with suggested
prevention and management strategies

Adverse event

Procedure

Evidence

Strategies to avoid or treat adverse event

Vascular compromise:

• arterial occlusion and transient ischaemia

• severe ischaemia, extremity necrosis and gangrene

For umbilical arterial catheter also includes:

• gluteoperitoneal necrosis ± sciatic nerve palsy

• spinal cord injury and flaccid paralysis

• increased risk of necrotising enterocolitis

Peripheral arterial catheter

Literature review of neonatal observational studies63

Neonatal case reports52 , 64 , 65

Regular monitoring of extremities for signs of vascular compromise66

Prompt catheter removal when no longer necessary66

Malposition is an important risk factor for umbilical arterial catheter ischaemic and thrombotic complications - high umbilical catheter position (T6 - 9) reduces the risk of ischaemic and thrombotic complications67

Vascular spasm is common and usually resolves within minutes.66 If persistent signs of vascular compromise detected, remove catheter immediately and consider:

• contralateral limb warming62

• 2% nitroglycerin application68

• sympathetic nerve blocks (e.g. brachial plexus)69

• surgical management as a last resort

Umbilical arterial catheter

Systematic review of effects of umbilical catheter position67

Neonatal case reports70 , 71

Refractory hypoglycaemia

Umbilical arterial catheter

Neonatal case reports72

Avoid umbilical arterial position near vessels supplying pancreas (T11 - L1) and avoid glucose containing umbilical arterial perfusate72

Increased risk of intraventricular haemorrhage

Umbilical arterial catheter

Slow withdrawal of blood samples (over at least 40 seconds)73

PICU = paediatric intensive care unit; NICU = neonatal intensive care unit.



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