Using Paralytic as Part of Premedication for Elective Intubation of Premature Neonates May Result in Transient Impairment of Ventilation

Transition to Routine Premedication for Nonemergent Intubations in a Level IV Neonatal Intensive Care Unit

We thank Fleishman et al for their study evaluating the implementation of a standard premedication for intubation in a level IV neonatal intensive care unit (NICU).[1] The authors used atropine and fentanyl as part of their regimen, while vecuronium (paralytic) was optional. They report that the implementation of premedication protocol resulted in decreased pain scores but not fewer intubation attempts.[1] The mean gestational age of infants intubated in this study was 37 to 39 weeks with a wide standard deviation (6.7–8.9 weeks). The number of extremely preterm and very low birth weight infants (VLBW) in this study was not specified. Lower gestation may increase the risk of adverse events associated with premedication. The authors provided data on pain scores but have not reported changes in oxygenation and ventilation.

The American Academy of Pediatrics (AAP) recommends using a vagolytic, analgesic, and/or hypnotic, with an option to use muscle relaxant. The ideal combination and/or sequence of premedications have not been established, although muscle relaxant when used should always be in conjunction with an analgesic.[2] Based on these recommendations, our institution incorporated an analgesic and a paralytic-based regimen using fentanyl and vecuronium/rocuronium. Fentanyl is the preferred analgesic, while vecuronium and rocuronium are muscle relaxants recommended by AAP.[2] We did not use a vagolytic agent as atropine may be associated with side effects in preterm infants with hypoxic bradycardia and can cause tachycardia in some neonates after intubation.[3] [4] On implementation, we found that preterm infants had transient respiratory impairment requiring increased respiratory support immediately after using premedication. Data collected on premature infants (<34 weeks) who underwent elective (n = 30, using premedication) and emergent intubation (n = 26, without premedication) between 2013 and 2015 in our NICU are shown in [Table 1]. Infants were emergently intubated if they were hypoxic and did not respond to noninvasive ventilation. Intubations in the delivery room and during transport were not included. Baseline information, time of intubation, ventilator settings, and blood gases are shown in [Table 1]. We used similar pressure setting and rates (∼40/min) immediately after both emergent and elective intubations, but infants who received paralysis eventually needed higher respiratory support ([Table 1]). There was no difference in blood pressures and saturations pre- and post-intubation. Following intubation, the use of paralytic resulted in increased carbon dioxide levels (p < 0.001) ([Fig. 1]). Frequent blood gases and noninvasive CO₂ monitoring were needed to stabilize these infants along with escalating ventilation settings (pressures/change of ventilation modes) to optimize ventilation similar to the experience reported by Durrmeyer et al.[3] They speculated that this might be secondary to the loss of lung recruitment during intubation resulting in decreased compliance and need for higher ventilator settings post muscle relaxant use. Based on this experience, our institution has moved away from using paralytics routinely in premature neonates as part of premedication. However, we did have two infants with chest wall rigidity (out of 12 infants) when fentanyl was used without paralysis. We request the authors to provide more information (including blood gas parameters) with the use of premedication involving paralysis (mentioned as optional in the regimen). There is a lack of evidence for the use of premedication in VLBW infants, and the available studies have relatively smaller sample sizes.[2] Prospective, randomized trials evaluating respiratory and neurodevelopmental outcomes with the use of paralysis during premedication for elective intubation in VLBW infants are needed.

Fig. 1 Change in carbon dioxide levels following intubation. The changes are shown in the figure as box plots. ^* p < 0.001 statistical significance for pCO₂ before and after intubation when paralysis was used as part of the premedication.

Table 1 Emergent intubation versus premedication with paralysis use in preterm infants

Parameters	Emergent intubation without premedication (n = 26)	Elective intubation with premedication with paralysis (n = 30)
Gestational age (wk)	30.2 ± 2.0	29.8 ± 3.2
Birth weight (kg)	1.54 ± 0.7	1.48 ± 0.5
Age at intubation after birth (d)	0.6 ± 0.6	0.7. ±  0.6
PIP after intubation (cm H2O)	20.3 ± 3.7	22.1 ± 2.7[a]
RR after intubation (per min)	40.4 ± 3.2	45 ± 5.6[a]
MAP after intubation (cm H2O)	9.4 ± 1.3	11.3 ± 1.8[a]
Mode of ventilation after intubation	Conventional 19, HFOV—7	Conventional 21, HFOV—9
FIO2	0.30 (0.25–0.45)	0.30 (0.24–40)
SpO2%	96 ± 3	94 ± 3

Abbreviations: FIO₂, fraction of inspired oxygen; HFOV, high-frequency oscillatory ventilation; MAP, mean arterial pressure; pCO₂, partial pressure of carbon dioxide; PIP, peak inspiratory pressure; RR; respiratory rate; SpO₂, peripheral capillary oxygen saturation.

Note: Data presented as mean and standard deviation.

^a p < 0.05 significantly different.

Authors' Contributions

P.C.: Collected data, analyzed, drafted the initial manuscript, reviewed, and approved the final manuscript as submitted. A.N.: Collected data, reviewed, and approved the final manuscript. M.R.: Collected data, reviewed, and approved the final manuscript. S.L.: Collected data, analyzed, reviewed, and approved the final manuscript as submitted. All authors approved the letter as submitted and agree to be accountable for all aspects of the work.

• References

• 1 Fleishman R, Mossabeb R, Menkiti O, Young M, Bains V, Cooperberg D. Transition to routine premedication for nonemergent intubations in a level IV neonatal intensive care unit. Am J Perinatol 2017; DOI: 10.1055/s-0037-1607282.
• 2 Kumar P, Denson SE, Mancuso TJ. ; Committee on Fetus and Newborn, Section on Anesthesiology and Pain Medicine. Premedication for nonemergency endotracheal intubation in the neonate. Pediatrics 2010; 125 (03) 608-615
• 3 Durrmeyer X, Dahan S, Delorme P. , et al. Assessment of atropine-sufentanil-atracurium anaesthesia for endotracheal intubation: an observational study in very premature infants. BMC Pediatr 2014; 14: 120
• 4 Kattwinkel J, Fanaroff AA, Klaus MH. Bradycardia in preterm infants: indications and hazards of atropine therapy. Pediatrics 1976; 58 (04) 494-499