Neonatal Research

Our tiny babies have very tiny tracheas. So far you are probably all with me. Putting that tube in the right position is therefore tricky. In particular avoiding the right mainstem bronchus, which is the wrong position, is important.

So first of all; where should the tip be? That seems obvious, it should be in the trachea, high enough above the carina that the tube never slips into the carina, but low enough that it doesn’t slip out. On a plain AP radiograph, however, it isn’t always clear exactly where the tube tip should be. In general ,studies have suggested that on the radiograph the tip of the tube should be T1-T2. That is based on studies where the position was directly observed, such as in post-mortem studies, and compared with an X-ray.

A study from 7 years ago (Thayyil S, et al: Optimal endotracheal tube tip position in extremely premature infants. American journal of perinatology 2008, 25(1):13-16.) noted that babies who had a tube tip lower than T1-T2 were more likely to have right upper lobe collapse, localized PIE and pneumothorax. I think that confirms that T1-T2 is the appropriate location.

Now how do we ensure that the tube tip is in that, optimal, position? The NRP (which clearly is not focussed on very preterm babies) suggests to add 6 cm to the infants weight in kg, which leads to tube insertion depths which are too low for most babies under 1 kg (see for example : Peterson J, et al: Accuracy of the 7-8-9 Rule for endotracheal tube placement in the neonate. J Perinatol 2006, 26(6):333-336.) I think it is clear we should not use that rule for babies under 1 kg.

Various methods of calculation have been suggested, some are based on calculations using the babies weight, some on gestation, one on foot length (which actually seems to be a good idea, and relatively easy to get to during resuscitation, but I don’t know if anyone does that. Embleton ND, et al: Foot length, an accurate predictor of nasotracheal tube length in neonates. Archives of Disease in Childhood – Fetal and Neonatal Edition 2001, 85(1):F60-F64) maybe Nick Embleton will let me know if anyone uses it.

A newly published trial from Colm O’Donnel in Dublin (Flinn AM, et al: Estimating the Endotracheal Tube Insertion Depth in Newborns Using Weight or Gestation: A Randomised Trial. Neonatology 2015, 107(3):167-172.) randomly compared weight and gestational age based standards, unfortunately the weight based standard they used was depth= weight + 6, and they compared this to a table based on gestational age. The number of ET tubes in the right place was higher with the weight calculation, but it was not statistically significant, and there were very many that were malpositioned in both groups, 50% with the weight based calculation, and 60% with the GA table.

Another study, which also trashed the 7-8-9 rule promoted by NRP, (Kempley ST, et al: Endotracheal tube length for neonatal intubation. Resuscitation 2008, 77(3):369-373) was a report of a quality improvement initiative in London. It is interesting in part because they showed that intubating the baby and then doing a clinical exam to see if  it was in the right place was associated with more than half of the ETTs being mal-positioned. While using a table of distances (either GA based or weight based) was much better, with less than 20% needing repositioning.

Colm O’Donnell has also published a letter with photos of endotracheal tubes (Gill I, O’Donnell CP: Vocal cord guides on neonatal endotracheal tubes. Archives of disease in childhood Fetal and neonatal edition 2014, 99(4):F344.) which clearly shows that you can’t rely on the ETT marks to decide where to put the tube. Non-one ever evaluated this previously, as far as I can tell in the literature, but using those marks will lead to many being in the wrong place. I think it should be obvious that all babies who are intubated with a 2.5 tube do not have the same length of trachea! So using the same ETT tube marking wll often be wrong.

So how best to do this?

I think that the first step should be to use a table of insertion depth against body weight. (we are a center which attracts a lot of extremely growth restricted babies, so I would be wary of using a GA standard). I think the table below looks to be the best (UPDATE** I failed to mention previously that the table is from the study which I refer to above by Stephen Kempley) , I have added a column for nasal intubation based on the demonstration (autopsy study,with body weights down to 500 g) that the distance from nostril to carina is almost exactly 1.2 cm on average longer than the distance from lip to carina (Rotschild A, Chitayat D: Optimal Positioning of Endotracheal Tubes for Ventilation of Preterm Infants. AJDC 1991, 145:1007.)

During the intubation procedure, prior to fixing the tube, palpation in the supra-sternal notch can confirm good tube position with very good accuracy, once you have been trained to do it. A randomized trial from Neil Finer’s group (Jain A, et al: A randomized trial of suprasternal palpation to determine endotracheal tube position in neonates. Resuscitation 2004, 60(3):297-302.) who showed me the technique when I was his fellow) found a much higher proportion of tubes in the right position after adequate training, and another RCT (Saboo AR, et al: Digital palpation of endotracheal tube tip as a method of confirming endotracheal tube position in neonates: an open-label, three-armed randomized controlled trial. Pediatric Anesthesia 2013, 23(10):934-939) had a high proportion of tubes in good position, 83%, following a process such as I have just described, a table of insertion depths, accompanied by palpation to validate position.

Here is that table:

((This is the initial length to which the tube should be inserted, followed by palpation of the tube to ensure good position, and then a chest radiograph to check its position. The tube length should then be adjusted to align its tip with the thoracic vertebrae T1–T2.))

Another important point, flexion of the neck advances the end of the ETT, but, in fact, the sze of the effect is fairly minor. A severe flexion of 55 degrees only advances the tube tip by about 3 mm (Rost JR, Frush DP, Auten RL: Effect of neck position on endotracheal tube location in low birth weight infants. Pediatric Pulmonology 1999, 27(3):199-202). So if the tube is on the carina when you do the x-ray and the head is flexed, you still need to reposition the tube, you can’t rely on good head position to move the tube tip up much.

Finally there are some data to support using ultrasound to confirm tube position, (Chowdhry R, Dangman B, Pinheiro JM: The concordance of ultrasound technique versus X-ray to confirm endotracheal tube position in neonates. J Perinatol 2015. Dennington D, Vali P, Finer NN, Kim JH: Ultrasound confirmation of endotracheal tube position in neonates. Neonatology 2012, 102(3):185-189.) It looks like this could be a reliable way of identifying malposition of the tube, and we should consider maybe training everyone to do this, including me!

After our amazing week in Apollo Bay, we said goodbye to the English contingent, and crossed over to the east side. Melbourne sits above a huge bay, known as Port Philip, we went as far as we could on the Great Ocean Road, and then crossed from the west to the east abord a ferry, and found ourselves, after passing over the Mornington peninsula, in Inverloch. We arrived in the middle of  a torrential downpour, but eventually installed ourselves in pleasant little shack, with occasional visits from Huntsman Spiders.

The week there was marked by visits to Philips Island, walks on Wilson’s Promontory, and eventually the Mornington Peninsula.

On Philips Island we met Pelicans, whose eyes are really weird, if you look closely into them…

And one of our walks, in particular, was spectacular, on Wilson’s promontory the scenery, and the wildlife are incredible:

On our way back from ‘the prom’ we stopped to find a huge mob of grey kangaroos, and we were buzzed by white-throated Needletails, shwooshing past us at over 100 kh/hr.

The kangaroos weird jewellery are from an on-going research project.

On the way back to Melbourne we stopped at Mont Alto, a beautiful and amazingly tasty vinyard, with many sculptures in the grounds, and well kept flower-gardens.

After a week in Noosa, we flew to Melbourne, then drove along the Great Ocean Road to Apollo Bay, or, in fact a few km before Apollo Bay. The house we rented was a few meters from the beach, and was the most amazing place I have ever been for wildlife. There was a dead tree in the garden which attracted a black-shouldered kite, flocks of Cockatoos, tree martins and starlings, the grassed parts of the garden attracted wrens, honeyeaters and various robins etc, and just by walking a few meters down to the beach there were plovers, herons, lapwings and others.

Here is a group of yellow-tailed cockatoos:

That is a black-shouldered Kite, here are two masked plovers:

and here is a view of that tree and the shore-line at the end of the day.

Another day while we were there, we were honored to receive a visit from a Koala:

We also went on a trip to see Platypus, my sister and my son swear they saw a platypus, all I can say is that I saw some beautiful birds, including this Nankeen Night-heron.

North of Sydney on the east coast on the Sunshine Coast of Australia is a town called Noosa. Noosa is a warm beautiful place to have a vacation, the town to my taste rather artificial, but it had the great advantage of a high-quality photography store. So replacing my, now clearly dead, camera was not too much of a hardship, except to my wallet.

The morning after our arrival in Noosa (and my trip to the camera store) we visited the Farmers’ market, where Annie had a mango salad which she still claims is one of the best things she has ever eaten, and where I saw my first Kookaburra!

Noosa, even though it is rather a tourist trap, is also very beautiful, and one of the most memorable walks of our trip was a hike through the Noosa national park.

Rainbow Lorikeets like this one are everywhere, and early in the morning there was frequently a flock of them passing our house.

We saw our first Koala, in a tree in the Noosa park, and many different birds, including this honeyeater which is known as a friarbird. 

In Sydney we were joined by other family members, the childrens’ two grandmothers, and my sister and her husband. Our first day was very hot, and we spent it close to the water, on ferries around the bay, and walking through the Botanical Gardens. Here is the classic Sydney photo, Opera House, Bridge and tall ship.

The obligatory Sydney photo is a photo of the bay for the simple reason that the bay is amazing. This was only my second time in Sydney, and it feels somewhat other-worldly, but a view of the harbour, is a unique and strikingly beautiful sight. I don’t know anywhere in the world quite like it.

For the rest of the week we explored Sydney. The 26th of January is both the Australian National Day, and my mother’s birthday. So as well as a great barbecue at a friend’s home (William Tarnow-Mordi is a great host), I was able to convince my mother that Sydney had put on fireworks for her 86th birthday.

The trip to Manley was one highlight, including the walk along the coast, and meeting the water dragons.

Later in the week we walked from Bondi Beach to Maroubra bay on a very blustery day.

The waves were unpredictable, when I was taking photos of Tai playing on the beach, there was a freak wave which knocked him over, and as I scrambled up from where I was (about 15 feet from the water’s edge I thought) trying to make sure he was alright, my camera was well-washed by sandy salt-water. Instant death (of the camera, not Tai, thank Odin) … Now what?

This is  a study of the hemodynamic profile of preterm infants who have septic shock, compared to matched controls. And an analysis of changes after institution of therapy.

Saini SS, Kumar P, Kumar RM: Hemodynamic changes in preterm neonates with septic shock: a prospective observational study. Pediatric critical care medicine: 2014, 15(5):443-450.

This is, I think, almost unique data. There is a previous study of the hemodynamic profile of infants who were thought to have sepsis (from Koert de Waal and Nick Evans) but not, like this study, restricted to that group of babies that are most problematic and high-risk, those in shock.

We really need data like these in order to be able to decide which kinds of therapy to test. I was, based on guesswork rather than data, of the opinion that septic shock in the newborn was often different to the kind of urosepsis that is a common cause of (usually gram negative) septicemia and warm shock in the adult. That was largely based on animal data, particularly data based on animal modelf of GBS sepsis .

This study using mostly echocardiography, along with clincial assessment, studied 52 preterm infants with a diagnosis of septic shock, half of whom had positive cultures. There were 52 infants matched for gestational and postnatal age who served as controls.

One thing these authors did not do was to divide the cases by cause of sepsis, I think it is likely, or at least possible, that gram negative organisms and their endtoxins lead to a differnet hemodynamic profile than gram positive organisms. Certainly in the studies I mentioned in newborn animals with GBS sepsis, they usually have a low cardiac output, and cold shock, which is a bit different to what these authors show, in their preterms. Of the 26 babies with positive cultures, 18 had gram negative organisms. I guess with only 8 ‘others’ (6 gram positives, 2 fungi) an analysis by type of organism would be problematic, but on the other hand it would have helped people to have preliminary data to see if enterococcal or staphylococcal sepsis might be different.

There are some findings, though, which are difficult to understand, for example, the study reports a substantially higher left ventricular output, LVO, in the septic babies than the controls, suggesting vasodilatation as an important cause of the shock, which is understandable, but at the same time, RVO was higher than LVO in both groups, and was essentially the same in the 2 groups, meaning that in the controls RVO was very much higher than LVO, while in the septic shock babies it was only slightly higher.

To have a right ventricular output so much higher than left is quite surprising. Usually, of course, with an open PDA and a left to right shunt, the LVO is higher than the RVO. If there are no shunts at all, the 2 are obviously equivalent. If the RVO is that much higher than the LVO, then maybe the control babies had large left-to-right inter-atrial shunts, which woud be strange, or large right to left PDA shunts, which also wouldn’t make a lot of sense.

Other published data are consistent with what I am saying here, for example, this study (Sirc J, Dempsey EM, Miletin J: Diastolic ventricular function improves during the first 48-hours-of-life in infants weighting <1250 g. Acta Paediatr 2015, 104(1):e1-6.) shows LVO consistently greater than RVO and increasing over the first 48 hours of life.

Which suggests to me that maybe there is a systematic error in the measurements by this group, inflating RVO. So we should treat these data with caution, and note that they suggest that vasodilatation is common in preterm babies with gram negative sepsis, or with negative cultures and similar clinical findings. But they can’t be considered definitive.

Further studies of the hemodynamics of septic shock are need to confirm these findings in the systemic circulation and clarify what is happening in the relative outputs of the 2 ventricles, and the circulatory shunts.

When we look at the effects of therapy, the authors were able to have before and after data from 41 septic babies who receive either dopamine or dobutamine. They didn’t show much in teh way of changes, apart from some increases in heart rate, particularly with dopamine.

More data about infants with septic shock would definitely help to determine which therapies are the most appropriate to study.

I have just added another batch of Australian Bird Photos, and reformatted the ‘Photos’ page on this blog.

Hope you like them: if you click on one of the photos you can see a high-resolution version.

Saying goodbye to New Zealand was tough. The amazing scenery, spectacular geothermal region, and unique wildlife, although expected, exceeded all my expectations. What was a bit unexpected was the sincere, open, friendliness of the people, we never met anyone who was not helpful and generous.  I don’t think that was just because we were foreigners, as we experienced the same attitude whether people knew we were visitors, or not. I don’t think I could manage to be so unfailingly good-natured, so maybe I wouldn’t fit in here.

I was also very impressed by the approach to environmental protection, which seems to be a priority for every decision that is made. Good luck to them, they have a great deal which is unique, and sorely needs protection. Half of the bird species that were endemic when the Maoris arrived are already extinct; most of those in the last few decades.

Which is an excuse for another series of photos: