In July 2016 I published a blog post No more intubating for meconium? Not quite. In this post I highlighted the recent recommendations to modify the approach to the non vigorous infant born through meconium. The traditional approach of electively intubating such infants for tracheal suctioning before beginning PPV was replaced by provision of PPV first. The rationale here was that delaying the establishment of ventilation while trying to intubate for most situations was more risky than just trying to establish a functional residual capacity (FRC). The naysayers pointed out that while this recommendation is possibly warranted for less experienced intubators, perhaps in the hands of those with more skill, tracheal suctioning would be the better option if it could on average be done quickly.
It has been over two years since that recommendation and change in practice. Isn’t it about time someone looked at whether or not this was a good thing to do?
A Comparison of Two Time Periods
Chiruvolu A et al published Delivery Room Management of Meconium-Stained Newborns and Respiratory Support in this month’s Pediatrics. In this paper the authors compared 4 hospitals with a retrospective period of one year before the NRP changes (October 1, 2015, to September 30, 2016) to a one year prospective period (October 1, 2016, to September 30, 2017) after implementation of the new guidelines. In the retrospective cohort there were 11163 mothers delivered at ≥35 weeks’ gestation. Meconium stained amniotic fluid (MSAF) was present in 1303 (12%) deliveries with 130 (10%) of newborns who were nonvigorous. During the prospective time period, a total of 10 717 mothers delivered at ≥35 weeks’ gestation. MSAF was noted in 1282 (12%) deliveries, yielding 101 (8%) newborns who were nonvigorous. Therefore the study compared these 130 newborns in the retrospective cohort to the 101 in the prospective time period. The authors note that aside from the approach to MSAF there were no changes in care during this time in the delivery room.
A few differences exist though in the cohorts that are worth mentioning that were statistically significant. Firstly, the incidence of preterm and post-term infants were both higher in the prospective cohort (both 6% vs 1%). Secondly, the incidence of fetal distress was higher in the prospective cohort 57% vs 43%. All of these factors would tend to favour the retrospective cohort doing better than the prospective and so the authors in their results controlled for these differences. Not surprisingly the rate of intubation in the retrospective group was 70% vs 2% in the prospective arm.
What were the results?
The results shown in table 3 in terms of the Odds ratios have been adjusted for the aforementioned differences of preterm post-term and fetal distress. There are several things here worth noting. The risk of admission was significantly higher for respiratory distress. Oxygen needs and mechanical ventilation along with surfactant therapy were also notably higher. One things that showed no difference at all was the mean apgar score at 1 and 5 minutes. This is an interesting finding given the hypothesis that drove the change in practice. If establishing an FRC is the goal of the intervention to provide earlier PPV then shouldn’t the retrospective group have worse apgars due to less effective resuscitation? Maybe or maybe not. This really depends on the staff in the resuscitation room at the 4 hospitals. It might be that the staff were quite skilled so the intubations may have gone smoothly with minimal reductions in FRC compared to the prospective group. What would this study look like if done in a centre with less experienced people capable of intubation.
Also interesting in this study is that when isolating comparisons to those admitted to the NICU and those specifically diagnosed with MAS there were no differences between groups for such outcomes as length of stay, oxygen therapy, mechanical ventilation (MV) or days of MV. Given that the group sizes though were quite small (7 and 11 for MAS) we do have to take this data with a grain of salt as it really is too small to make any certain conclusions. A larger study would need to be done looking at these types of outcomes to really get a better handle on whether the approach to MSAF matters to these individual outcomes.
What this study does for me is raise an eyebrow. The change in practice does not seem to yield “better babies”. Secondly what we do see even when controlling for differences that would affect hospital admissions for respiratory distress is an increase in admission rate. In times when beds are becoming increasingly precious as census for many units swell one has to ask whether this approach is truly the better way to go. Perhaps it was wrong for the NRP to declare that for all practitioners it is best to provide PPV rather than intubate. This may have been too simplistic. If you have experienced intubators perhaps it would be best to continue to intubate first in this setting rather than provide PPV. What this study does is certainly raise questions and begs for a larger study to be done to determine whether these results can be replicated. If they are then I suspect the NRP may be headed down a different path for recommendations yet again.
After the recent CPS meeting I had a chance to meet with an Obstetrical colleague and old friend in Nova Scotia. It is easy to get lost in the beauty of the surroundings which we did. Hard to think about Neonatology when visits to places like Peggy’s Cove are possible. Given out mutual interest though in newborns our our conversation eventually meandered along the subject of the new NRP. What impact would the new recommendations with respect to meconium have on the requirements for providers at a delivery. This question gave me reason to pause as I work in a level III centre and with that lens tend to have a very different perspective than those who work in level I and II centres (I know we don’t label them as such anymore but for many of you that has some meaning). Every delivery that is deemed high risk in our tertiary centre has ready access to those who can intubate so the changes in recommendations don’t really affect our staffing to any great degree. What if you are in a centre where the Pediatrician needs to be called in from home? Do you still have to call in people to prepare for a pending delivery of a baby through meconium stained fluid?
What does the new recommendation actually say?
These recommendations are from the American Heart Association and are being adopted by the NRP committees in the US and Canada. The roll-out for this change is coming this fall with all courses required to teach the new requirements as of September 2017.
“However, if the infant born through meconium-stained amniotic fluid presents with poor muscle tone and inadequate breathing efforts, the initial steps of resuscitation should be completed under the radiant warmer. PPV should be initiated if the infant is not breathing or the heart rate is less than 100/min after the initial steps are completed. Routine intubation for tracheal suction in this setting is not suggested, because there is insufficient evidence to continue recommending this practice. (Class IIb, LOE C-LD)“
The rationale for the change is that is that there is a lack of evidence to demonstrate that routine suctioning will reduce the incidence of meconium aspiration syndrome and its consequences. Rather priority is placed on the establishment of adequate FRC and ventilation thereby placing a priority on teaching of proper bag-valve mask or t-piece resuscitator. Better to establish ventilation than delay while atempting to intubate and run the risk of further hypoxia and hypercarbia causing pulmonary hypertension.
Does this mean you don’t need to have a person skilled in intubation at such deliveries?
This question is the real reason for the post. At least from my standpoint the answer is that you do in fact still require such people. This may seem to be in conflict with the new position but if you move past that recommendation above you will see there is another line that follows afterwards that is the basis for my argument.
“Appropriate intervention to support ventilation and oxygenation should be initiated as indicated for each individual infant. This may include intubation and suction if the airway is obstructed.”
While we should not routinely perform such intubations there may be a time and a place. If one has intiated PPV with a mask and is not obtaining a rising heart rate, MRSOPA should be followed and attempts made to optimize ventilation. What if that is unsuccessful though and heart rate continues to be poor. You could have a plug of meconium distal to the vocal cords and this is the reason that intubation should be considered. In order to remove such a plug one would need to have an intubator present.
Where do we go from here?
As much as I would like to tell my colleague that he doesn’t need to have this skill set at a delivery for meconium I am afraid the skill still needs to be present. It will be interesting to see how instructors roll this out and answer such questions. It is a little concerning to me that in our world of wanting the “skinny” or “Coles’ Notes” version of things, the possibility of still needing the intubator on short notice may be lost. Having someone on call who is only “5 minutes away” may seem to be alright but at 3 AM I assure you the 5 minutes will become 15 as the person is woken, dresses, gets to the car and parks. Whether it is 5 or 15 minutes each centre needs to ask themselves if the baby is in need of urgent intubation are you willing to wait that amount of time for that to happen?
We live in a world at the moment where the public has become increasingly aware of the dangers of antibiotic overuse. Parents are more than ever requesting no erythromycin for the eyes after birth, and even on occasion questioning the need for antibiotics after delivery for the infant with risk factors for sepsis. The media has latched on to the debate as well by publishing the sensational articles about superbugs and medicine running out of the last lines of defence such as this article from the CBC.
As teams caring for newborns both preterm and term we are also increasingly aware of the dangers of altering the microbiome of these vulnerable infants with antibiotic overuse. Some babies robbed of the vaginal microbiome when delivery occurs by C-section, have their parents swabbing their newborn with vaginal secretions to populate their child with the “good bacteria” that come through a “natural” delivery although recent commentary questions the safety of such practice.
Infants born through meconium stained amniotic fluid can certainly become sick after delivery. Inhalation of meconium in the sickest infants often occurs during gasping episodes in utero after hypoxic stress causes evacuation of the rectal contents. The fetuses who inhale this material may go on to develop, inflammatory changes, areas of atelectasis and hyperinflation and pulmonary hypertension; the so called meconium aspiration syndrome. These infants of course may be extremely sick and need high frequency ventilation to manage their CO2 retention and in some cases may go on to ECMO although with inhaled nitric oxide this has become less common. As another consideration, could infection such as chorioamnionitis be the inciting event to cause passage of meconium in utero?
The health care team though for as long as I have been in practice would add to the treatment plan a course of antibiotics. In fact I would guess that many Neonatologists the world over have uttered the phrase “They are REALLY sick, please start antibiotics”. The real question though is whether the baby is in fact infected. Meconium is certainly a good growth medium for bacteria but with the short time from passage to delivery in most cases I doubt there is much time for significant growth. Moreover, I have found myself saying many times that such infants have a chemical pneumonitis and have often questioned whether antibiotics are really needed. Nonetheless it would take nerves of steel in some cases to not use antibiotics in these patients.
Then along came this study
Role of prophylactic antibiotics in neonates born through meconium-stained amniotic fluid (MSAF)—a randomized controlled trial by Goel A et al. This study was done prospectively by randomizing newborns born through meconium stained amniotic fluid to either antibiotics (N=121) for three days or no antibiotics (N=129) after diagnosis. In each case blood and CRP were drawn and if the infant was symptomatic (presence of respiratory distress, lethargy, abdominal distension, temperature or hemodynamic instability, hypoglycemia, apnea, or any other systemic abnormalities) a lumbar puncture and chest x-ray were added. The primary outcome variable was defined as ” the incidence of early (within first 72 h of birth) or late onset (after 72 h of birth) suspect sepsis (clinical symptoms or positive sepsis screen defined as ≥2 positive parameters) and confirmed sepsis (positive blood culture).”
Clinicians in the study were allowed to continue antibiotics past the 72 hours or start antibiotics in the no antibiotic group if they considered an infant to have suspected sepsis or in fact were found to be proven. The outcomes for those possibilities are shown below.
Taking it all together whether you started antibiotics or not the primary outcomes were no different. Furthermore there is no apparent harm based on outcomes that matter including the most important; death (3 in each group) that it does give one reason to pause when considering whether to treat prophylactically with antibiotics for babies born through meconium stained fluid.
What About The Sickest of The Sick
When attempting to answer this question the authors noted the following.
“On doing a subgroup analysis on incidence of sepsis in symptomatic babies (presenting with respiratory distress), both groups were found to have comparable incidence of suspect sepsis (p=0.084). The incidence of confirmed sepsis was more in symptomatic babies, although the total numbers was very few (p=0.01)”
Herein lies the challenge in declaring once and for all that we don’t need antibiotics at all in MAS. While the study was powered to adequately answer the primary outcome, the subgroups are so small that declaring with any confidence that one can stand by and watch infants with severe MAS without starting antibiotics is a tough conclusion to come to. The child though who is born through MSAF and has mild tachypnea as the only symptom I suspect is another story. I might even argue that the baby who is in need of CPAP could be watched and if they deteriorate have antibiotics started. As much as I would love to say none of these babies need antibiotics I would have to admit that I would cave once the baby was ventilated. It is better to provide a couple of days of antibiotics while awaiting blood cultures than to have a patient with sepsis left untreated or at least that is my opinion.