Cannula and Co.: Friendly Bloodsuckers

16. August 2016

Whether it be blood extraction or vaccination, a prick and a small amount of pain is part of the deal – or at least until now. But the anaesthetic patch, infrared technology and blood sample extraction performed without using a cannula are making routine procedure easier and more bearable for the patient.

In Scandinavia barely a vaccine or blood test is carried out without anaesthetic patches. According to STIKO recommendations, at least eight to ten vaccinations take place in the first 24 months of a newborn’s life. This is often the cause of many tearful appointments at the paediatrician’s office – yet it does not need to be so. Using a local anaesthetic cream or an active ingredient patch, injections and blood sample extractions can be done virtually painlessly.

Consolation patch with two agents

Percutaneous anaesthesia is done using lidocaine and prilocaine. Only the free bases of local anaesthetics are able to diffuse through the cell membrane. The actual effect is shown by the active compounds in ionised form on the inside of the cell membrane at the receptors in the fast sodium channel areas.

Therefore a pharmaceutic trick has to help in overcoming the barrier. After producing a 1:1 mixture of the two substances in powder form, lidocaine and prilocaine as bases experience a drop in their melting point from 67 °C (lidocaine) or 37 °C (prilocaine) to 18 °C. There is an oil formed which is displaced using a thickening agent, an emulsifier, and distilled water. This results in a oil-in-water emulsion in which both the local anaesthetics are present as much as 80% in the base form. The point in the prilocaine and lidocaine phase diagrams with the lowest melting point is called the eutectic point. The mixture with a defined composition at this point is an eutectic mixture. From this comes the name of the medicinal product: EMLA stands for “eutectic mixture of local anaesthetics”.

It is important to apply the cream sufficiently thick. For pain prevention in the event of skin punctures, the recommendation for use on infants is 0.5 g over 5 cm2, for children 1 g over 10 cm2 and for use on adults 1.5 – 2 g over 10 cm2 .

The required reaction time depends greatly on the application site and the desired analgesic depth. For most areas of the skin, the required contact time is at least one hour; this time should not exceed four hours. If the film and the cream are removed within this time window, the anaesthesia still lasts for about an hour. The active analgesic depth after one hour is about 3 mm and after two hours a maximum of 5 mm. In mucosal areas, ten minutes’ exposure attains the effect .

Sugaring and sucking

The pain of infants can nonetheless also be relieved using simple “home remedies”. For a long time it has been known that sugar solutions, distraction and breastfeeding reduce pain, both before and after vaccination or taking a blood sample. Already 16 years ago, an extensive research contribution of more than ten pages on this topic appeared, taking in 100 literature references on the subject.

Pain assessment in infants and young children is complex; a simple pain scale is insufficient for analysis. One distinguished option is PIPP score (premature infant pain profiles). This takes into account, when dealing with pain in infants, gestational age, state of consciousness, heart rate, blood pressure, eyebrow arching, eyes pinching and nasolabial fold as prameters.

A placebo-controlled study by Slater et al. examined the effect of sucrose solution with analgesia use prior to venipuncture in infants. In the literature, various sugar solutions are used, in addition to sucrose, and glucose solutions. Employing PIPP score the difference between groups was significant. In the sucrose group the average was 5.8; in the placebo group 8.5. After use of sucrose none of the children showed changes in expression, versus 35 percent of children in the control group.

One Indian study examined 180 newborns on the effect of a 30 percent sucrose solution, non-nutritive suckling (NNS), a combination of both methods, and placebo. Depending on whether the suckling process is connected with food intake or not, there is differentiation between nutritive sucking (breastfeeding, milk bottle) and non-nutritive sucking (pacifiers, fingers, nipple).

The measures were carried out two minutes before taking a blood sample from the heel. In the placebo group the children cried out on average for 416 seconds, in the group in which the children were given sucrose and suckled, they did not cry out at all; in the “suckling group” without sucrose, the children cried for 9 seconds. The combination of suckling and sucrose is thus most effective. The authors warned about the use of honey in poorer countries in place of sucrose solution. They see a danger of honey-mediated infant botulism and appealed to the industry to make inexpensive formulations available. A sterile 24-percent sucrose solution costs about one euro in Germany.

A Cochrane meta-analyse examined 47 studies involving a total of 7,049 infants and concludes that sucrose significantly reduces pain before a vaccination or blood extraction with neonatals and is free of side effects. In a study by Hatfield et al the effect of sucrose was studied in two to four-month old infants. Compared with placebo, the sugar solution reduced pain by 80 percent. In a study by Lemyre et al. it was investigated as to whether a 4-percent tetracaine gel amplified the way glucose had effects before venipuncture. Amazingly, this was not the case.

Endorphin, dopamine or just facial expression superficialities?

Why it is that sucrose and/or NNS has analgesic effects has been pursued by Naughton et al.. The calming and analgesic effect of sucrose is attributed to endorphin-releasing processes. NNS presumably acts due to non-endorphin-based orotactile stimulation. The authors conclude that the combination of sucrose with NNS may be considered safe for use with early and timely newborns to achieve pain relief when performing painful procedural interventions.

A study by Gradin et al. pursued the question of how sugar has analgesic and sedative effects, and they presume that there is influence involving dopaminergic and cholinergic pathways. In other words an activation of the reward system, which accounts for the pain reduction.

A completely different, amazing statement comes from the working group led by Slater et al. Sugar solution does not work at all as a central analgesic, but only changed the facial gesture of the infants. This would have negative influence on the pain scales. After a painful stimulus, evoked potentials occur in the EEG, something which has also been documented in the study. These pains-triggered changes occurred in the sucrose group as well. However these results do not coincide with many other results, including the cry-duration of the probands.

The most frequently expressed assumption is that the release of endorphins is a factor. However, this refutes an earlier study by Gradin et al. which was a randomised, placebo-controlled, double-blind study involving infants (N = 30) who had received before their sugar administration 0.01 mg / kg of opiate antagonists naloxone in intravenous form. An analgesic effect was established, in terms of heart rate and scream duration. This was not affected by the administration of antagonists, so that the endorphin theory is dispensed with.

According to the data, sugar solutions reliably reduce pain perception in infants. Although there is still speculation about the mechanism of action, it is advisable in any case to routinely apply these cost-effective method in paediatrics.

Illuminated veins

In order to keep pain outcomes due to blood sampling as low as possible, it is also important to strike the vein with the first prick. Good veins, poor veins or even rolling veins – this dread has a name in the societies of medical assistants. Although these mythical arterial abnormalities may not even exist, finding a vein can sometimes be problematic.

Illuminated veins

Illuminated veins thanks to new technology © Christimed

But there is help available here and it sounds like science fiction: a device the size of a tetrapack is directed at the patient’s arm and with crystal clarity, and in colour, there emerge peripheral or even deeper veins. Particularly in paediatrics, emergency medicine, or with obese patients, this has advantages. This option is made possible by means of infrared technology. The near infrared light absorbs the haemoglobin in the blood and thus indicates the course of the veins in precisely visible form. The vein pattern is projected by a DLP projector directly onto the skin of the patient. Using a special mode, peripheral veins, which are up to 10 mm under the skin, or the progressive course of veins up to 15 mm below the skin, can be displayed.

Another technique uses LED technology and costs a tenth of the infrared devices. The Australian Red Cross is testing the technique on blood donors, thus attempting to increase the rate of willing donors. Waller et al investigated in a study whether they have achieved success.

With the use of vein visualisation technology(VVT), the apprehension of young blood donors aged 18 to 30 years is supposed to be removed, any nausea suppressed, and the donor rate be increased. However, this has not been achieved. There is also work being done on cost-effective solutions, such as using tablet PCs or smartphones, according to an overview article by Juric et al.

Google sucking out all kinds of data – sometime soon blood as well?

The next step in blood collection systems are systems entirely free of needles. Google has patented a technological process using vacuum and microparticles. In particular for diabetics this should thus allow painless blood sampling. The patent application describes a blood collection system that sends a gas jet into a vessel involving microparticles which penetrates the skin. Further details are not yet known.

In collaboration with Novartis, the IT group is also developing a contact lens for diabetics which continuously measures the blood sugar level and conducts this to a smartphone. The glucose monitoring system FreeStyleLibre is already to be found on the market. The system consists of a sensor which sits on the upper arm, and which needs to be replaced every two weeks, and a reading device through which the values are read.

Absorption power without prick

A startup based in the United States has developed a device for collecting blood (HemoLink®) which creates a vacuum and can remove the smallest amounts of blood through capillaries without the use of a cannula. For a laboratory test, these amounts are often sufficient. After two minutes, the absolutely painless procedure is over. The device is supposed to be going on the market by the end of 2016 and in the view of the US research minister was worth providing with a financial injection of three million dollars, and without any cannula needed.

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