Association of full premedication on tracheal intubation outcomes in the neonatal intensive care unit: an observational cohort study

doi:10.21203/rs.3.rs-2252716/v1

Download PDF

Article

Association of full premedication on tracheal intubation outcomes in the neonatal intensive care unit: an observational cohort study

https://doi.org/10.21203/rs.3.rs-2252716/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Objective: Evaluate the association of short-term tracheal intubation (TI) outcomes with premedication in the NICU.

Study Design: Observational single-center cohort study comparing TIs with full premedication (opiate analgesia and vagolytic and paralytic), partial premedication, and no premedication. The primary outcome is adverse TI associated events (TIAEs) in intubations with full premedication compared to those with partial or no premedication. Secondary outcomes included change in heart rate and first attempt TI success.

Results: 352 encounters in 253 infants (median gestation 28 weeks, birth weight 1100g) were analyzed. TI with full premedication was associated with fewer TIAEs aOR 0.26 (95%CI 0.1-0.6) compared with no premedication, and higher first attempt success aOR 2.7 (95%CI 1.3-4.5) compared with partial premedication after adjusting for patient and provider characteristics.

Conclusion: The use of full premedication for neonatal TI, including an opiate, vagolytic, and paralytic, is associated with fewer adverse events compared with no and partial premedication.

Health sciences/Health care/Paediatrics

Health sciences/Medical research/Outcomes research

Neonatal tracheal intubation (TI) is a challenging procedure (1–4) with a high risk of adverse TI associated events (TIAEs) (3, 5, 6). Physiologic changes associated with failed intubation attempts may contribute to overall neonatal morbidity and increase the likelihood of adverse long-term developmental outcomes (5–10). Identifying methods to avoid vital sign instability and improve success during neonatal intubation has been the source of many investigations.

Intubation premedication, including analgesics, vagolytics, and paralytics, has been shown to improve TI success and reduce adverse events (2, 4–6, 11, 12). The vagolytic atropine mitigates vagally induced bradycardia, reduces oral secretions, and may minimize hypoxemia during TI when paired with paralysis (6, 11). Analgesics such as opioids are used to reduce the discomfort of intubation. Morphine is a commonly used opiate for pain control in the neonatal population. However, the rapid onset and short duration of the synthetic opiate fentanyl make it a better choice for TI (6, 11). Using a paralytic may contribute to a more controlled environment for intubation and optimize the position and view of the airway landmarks (3, 4, 6). The ideal paralytic is one with quick onset and short duration of action, improving the outcome of intubation without eliminating a neonate’s spontaneous ventilatory drive for a prolonged time (6, 11, 13).

While premedication has been recommended for non-emergent neonatal TI (11), there remains considerable practice variation among Neonatal Intensive Care Units (NICUs) (2–6, 8, 14–18). In a recent manuscript from the National Emergency Airway Registry for Neonates (NEAR4NEOS), Ozawa et al. found significantly fewer TI attempts and improved first attempt success for intubations performed with opiate sedation and a paralytic compared with intubations performed without medications (4). However, they did not specifically evaluate the use of atropine in combination with opiate sedation and paralysis.

We conducted an observational cohort study to evaluate the association between premedication and short-term TI outcomes. We aimed to compare TI using an opiate analgesic, vagolytic and paralytic (full premedication) with TI using a partial combination of premedication or no medications. We hypothesized that intubations with full premedication would have fewer TIAEs and higher first attempt success rates than intubations with partial or no premedication.

Setting and Design

This observational cohort study was performed at a single academic NICU using prospectively collected data from NEAR4NEOS, a multicenter collaborative with the goal of improving neonatal intubation safety (19, 20). The University of Washington Medical Center (UWMC) is a 49-bed, level IV NICU with a delivery service of approximately 1 900 deliveries each year. The UWMC has participated as a clinical site within the NEAR4NEOS collaborative since 2016. The NEAR4NEOS data collection form captures patient, practice, provider, and TI outcome data for delivery room and NICU intubations as described in standard operational definitions (19, 20). Data forms are filled out immediately following each intubation by the provider(s) performing the intubation. For accuracy, research assistants audit all data forms and input data into a secure Research Electronic Data Capture (REDCap). This study was approved by the Seattle Children’s Institutional Review Board (IRB # 14922).

Data collection and operational definitions

Data were collected from all in-unit TI encounters between June 2017 and December 2021. The NEAR4NEOS defines an intubation encounter as one advanced airway management event and an intubation course as one method or approach to securing the airway (e.g., oral or nasal) (19, 20). A single TI encounter may have multiple courses, and some infants in the cohort had multiple TI encounters within the data collection period. We included only the first course of each TI encounter as data from subsequent courses may not be independent of each other (4). We included the medications administered prior to the first TI course. We excluded TIs performed in the delivery room or in the setting of unstable hemodynamics, such as ongoing Cardiopulmonary Resuscitation (CPR), as premedication is not indicated during those circumstances.

Adverse Tracheal Intubation Associated Events

The NEAR4NEOS defines TIAEs as any unwanted outcome or event that occurred because of the intubation or observed during or after the intubation (3, 19). We followed standard operational definitions, grouping TIAEs into severe and non-severe categories (3, 4, 20). Vital sign data collected by the intubating team includes the highest pulse oximetry and heart rate reading immediately before the first TI attempt and the lowest pulse oximetry and heart rate reading during the course. Severe oxygen desaturation was captured separately from TIAE and defined as 20% decrease from the highest oxygen saturation (SpO₂) during the intubation course (4). The heart rate difference was defined as the absolute change in heart rate during the first TI course.

Premedication

During the study period, the UW NICU underwent practice changes to enhance the use of premedication for non-emergent TI. Practice changes included creating an intubation medication order set order set with atropine, fentanyl, and rocuronium premedication. The choice of premedication was at the discretion of the intubating provider. For this study, Full premedication was defined as opiate analgesia (morphine or fentanyl) with a vagolytic (atropine) and paralytic (rocuronium or vecuronium). Partial premedication was defined as opiate and/or vagolytic, and/or paralytic. Intubations performed without premedication (no vagolytic, opiate, or paralytic) were defined as No premedication.

Outcomes

The primary outcome is the incidence of adverse tracheal intubation associated events (TIAE). Secondary outcomes included change in heart rate during the intubation course, severe oxygen desaturation, and intubation success (first attempt success and number of intubation attempts).

Statistical Analysis: We evaluated the primary and secondary outcomes across three premedication groups: full premedication, partial premedication, and no premedication, as defined above. Using SAS® OnDemand for Academics (Cary, NC: SAS Institute Inc.), we generated descriptive statistics, including median and interquartile range (IQR) for nonparametric variables. Patient characteristics and intubation practice measures were compared across three groups. Continuous variables such as age, weight, and heart rate were analyzed between groups using one-way Analysis of Variance with post-hoc comparisons using the Tukey’s honestly significant difference (HSD). The Kruskal-Wallis test was used for nonparametric variables. Categorical variables such as patient, practice, provider characteristics, and TIAEs were compared between groups using Chi-square testing. A multivariable logistic regression model was used to adjust for confounding variables known to impact intubation success and safety, such as age at intubation, weight at intubation < 1.5 kg, comorbidities (history of a difficult airway, acute or chronic respiratory failure), intubation indication (frequent apnea or bradycardia, elective procedure, or reintubation after unplanned extubation, surfactant delivery), and the device used (direct or video laryngoscopy). After visual confirmation of heteroscedasticity of residuals when performing multivariable linear regression to evaluate heart rate difference during intubation across three groups, it was decided to perform the analyses using quantile regression adjusting for similar covariates as listed above. For all analyses, a p-value of < 0.05 was considered statistically significant.

Cohort Characteristics

352 intubation encounters in 253 infants were analyzed (Fig. 1). The median gestational age was 28 weeks (IQR 25–32), and the median birth weight was 1.1 kg (IQR 0.7–1.9). Detailed description of the full, partial and no premedication groups may be found in Table 1. A total of 206 encounters included opiate analgesia (n = 116, 56% morphine, n = 90, 44% fentanyl). Of the 82 TIs with a paralytic, 23 (28%) included vecuronium and 59 (72%) rocuronium. A total of 212 or 89% of encounters using any premedication used the vagolytic atropine specifically as a premedication (Fig. 1).

Table 1

Patient, Provider, and Practice Characteristics by Premedication Group
Patient Characteristics N = 352 TI encounters	FULL Premedication N = 81, 23%	PARTIAL Premedication N = 157, 45%	NO Premedication N = 114, 32%	p-value
Age, days
0 days	16 (20%)	36 (23%)	48 (42%)	< 0.001
1–6 days	21 (27%)	60 (38%)	30 (26%)	0.05
7–27 days	18 (22%)	33 (21%)	21 (18%)	0.79
\(\ge\) 28 days	23 (28%)	22 (14%)	12 (11%)	0.002
Weight, kg	1.7 (0.9, 2.5)	1.0 (0.8, 1.7)	1.2 (0.8,1.8)	< 0.001
Male	48 (59%)	98 (62%)	61 (54%)	0.34
Comorbidity¹
History of difficult airway	8 (10%)	10 (6%)	4 (4%)	0.19
Sepsis	7 (9%)	10 (6%)	5 (4%)	0.48
Airway or craniofacial anomaly	2 (2%)	3 (2%)	2 (2%)	0.94
Acute respiratory failure	53 (65%)	124 (79%)	90 (79%)	0.05
Chronic respiratory failure	21 (26%)	27 (17%)	14 (12%)	0.05
Intubation Indication
Oxygen failure²	17 (21%)	35 (22%)	19 (17%)	0.51
Ventilation failure³	23 (28%)	41 (27%)	29 (25%)	0.89
Frequent apnea and bradycardia	18 (22%)	50 (32%)	12 (11%)	< 0.001
Procedure (e.g., ROP⁴ surgery, MRI⁵)	12 (15%)	4 (3%)	0	< 0.0001
Reintubation after unplanned extubation	3 (4%)	11 (7%)	27 (24%)	< 0.0001
Surfactant administration	18 (22%)	49 (31%)	42 (37%)	0.08
Intubate, Surfactant, Extubate (INSURE)	0	31 (26%)	28 (31%)	< 0.0001
Provider and Practice Characteristics
Primary airway provider⁶
Pediatric resident	15 (18%)	27 (17%)	18 (16%)	0.56
Neonatology fellow	36 (44%)	54 (35%)	45 (39%)
Neonatology attending	4 (5%)	3 (2%)	2 (2%)
Nurse practitioner, PA	21 (27%)	60 (38%)	39 (34%)
Hospitalist	5 (6%)	13 (8%)	10 (9%)
Intubation device
Direct laryngoscope	61 (75%)	136 (87%)	109 (96%)	< 0.001
Video laryngoscope	20 (25%)	21 (13%)	5 (4%)	< 0.001

Values presented as patient N (%) or median (IQR)

Data represents the first intubation course per TI encounter

Full premedication: opiate analgesia and vagolytic and paralytic

Partial premedication: opiate analgesia and/or vagolytic, and/or paralytic

No premedication: no opiate, vagolytic, or paralytic

¹More than one comorbidity and indication could be reported per patient

²Oxygen Failure is defined as PaO₂ <60 mm Hg in FiO2 > 0.6 in the absence of cyanotic heart disease

³Ventilation Failure is defined as PaCO₂ >50 mm Hg in the absence of chronic lung disease

⁴Retinopathy of Prematurity (ROP)

⁵Magnetic Resonance Imaging (MRI)

⁶Provider intubating on the first attempt

Neonates in the group receiving full premedication were more commonly older (\(\ge\)28 days at intubation) and larger at the time of intubation. In contrast, intubations performed on the day of birth were more likely to use no medications (Table 1). Before an elective procedure (e.g., Magnetic Resonance Imaging (MRI) or retinopathy of prematurity (ROP) surgery), full premedication was used significantly more often than partial or no premedication (full n = 12, 15%, partial n = 4, 3%, and no premedication n = 0, p < 0.0001). There were no significant differences in the provider intubating on the first attempt between groups (Table 1). Most intubations used direct laryngoscopy (n=306, 87%). TI using the video laryngoscope was more likely to be done with full compared with no premedication (n = 20, 24% vs. n = 5, 4%, p < 0.01).

Primary outcome:

Adverse TI associated events (TIAEs) occurred in 32% of all encounters. Non-severe and severe adverse events were noted in 91 (26%) and 23 (7%) of encounters, respectively. While the non-severe TIAE of ‘dysrhythmia’ includes tachycardia, bradycardia with heart rate < 60 bpm and other arrhythmias, 98% (40/41) of the cohort with ‘dysrhythmia’ during TI had bradycardia < 60 bpm (Table 2). In the univariate analysis, infants intubated with full premedication had fewer TIAEs (p < 0.001), including dysrhythmia (p < 0.0001) when compared to those intubated with no premedication (Table 2 and Fig. 2). When adjusting for confounding factors in the multivariable logistic regression model, the adjusted odds of any adverse TIAE was significantly lower for those neonates intubated with full premedication compared to infants who received no premedication (aOR 0.26 (95% CI 0.1–0.6), p < 0.001) (Fig. 3A).

Table 2

Univariate analysis of primary and secondary outcomes
Outcomes n (%) N = 352 TI encounters	FULL Premedication N = 81, 23%	PARTIAL Premedication N = 157, 45%			Full vs. Partial
Any TIAE	14 (17%)	51 (32%)	46 (40%)	P < 0.001	P = 0.01
Severe TIAE:	3 (4%)	12 (8%)	8 (7%)	NS	NS
Pneumothorax	0	1 (1%)	1(1%)	NS	NS
Non-severe TIAE:	11 (13%)	41 (26%)	39 (34%)	P = 0.001	P = 0.03
Mainstem intubation	4 (5%)	12 (8%)	2 (2%)	NS	NS
Esophageal with immediate recognition	6 (7%)	18 (12%)	9 (8%)	NS	NS
Esophageal with delayed recognition	3 (4%)	9 (6%)	3 (3%)	NS	NS
Dysrhythmia¹	1 (1%)	10 (6%)	30 (26%)	P < 0.0001	NS
Heart Rate Change and Desaturation:
Mild (lowest heart rate < 100 bpm)	7 (10%)	36 (24%)	54 (52%)	P < 0.0001	P = 0.02
Severe (lowest heart rate < 60 bpm)	0	10 (7%)	30 (29%)	P < 0.0001	P = 0.03
> 40% decrease from highest heart rate	7 (10%)	34 (23%)	44 (43%)	P < 0.0001	P = 0.03
Severe oxygen desaturation²	38 (49%)	86 (57%)	41 (41%)	NS	NS
Intubation Success:
First attempt success	40 (49%)	47 (30%)	46 (40%)	NS	P = 0.003

Full premedication: opiate analgesia and vagolytic and paralytic

Partial premedication: opiate analgesia and/or vagolytic, and/or paralytic

No premedication: no opiate, vagolytic, or paralytic

¹Dysrhythmia includes tachycardia, bradycardia with heart rate <60 bpm, and other arrhythmias

²Severe oxygen desaturation is defined as 20% or more absolute change from the highest oxygen saturation during the intubation course.

Secondary outcomes:

Change in heart rate during intubation: The median highest heart rate at the start of the intubation was 159 bpm (IQR: 140, 170) for those infants receiving no premedication, 170 bpm (IQR: 156, 182) for partial, and 179 bpm (IQR: 166,190) for the full premedication groups. The median lowest heart rate during intubation was 96 bpm (IQR: 55,130) for no premedication, 140 bpm (IQR: 106,154) for partial, and 158 bpm (IQR: 139, 173) for full premedication groups. During the intubation course, the average change in heart rate was 35 bpm greater (95% CI 20–52) for those neonates intubated without premedication compared to those infants receiving full premedication.

Overall, there were fewer instances of mild or severe change in heart rate (lowest heart rate during intubation < 100 bpm or < 60 bpm, respectively) during intubation with full compared to no premedication in both the univariate and multivariate models (Table 2 and Fig. 3B). Within the full premedication group, only 7 (10%) TI encounters had greater than 40% decrease in heart rate from the highest heart rate recorded during the TI course, compared with 34 (23%) in the partial and 44 (43%) in the no premedication group (full vs. partial: P = 0.02, full vs. none: P < 0.0001).

First Attempt Intubation Success was greater for intubations using full premedication compared to partial premedication on univariate analysis (n = 40, 50% vs. n = 47, 29%, p = 0.002) and multivariate analysis adjusting for factors such as age and weight at intubation, history of a difficult airway and intubation indication (frequent apnea or bradycardia, elective procedure, or reintubation after unplanned extubation, surfactant delivery), as well as the device used (direct or video laryngoscopy) (aOR 2.7 (95% CI 1.3–4.5), p = 0.002) (Fig. 3C). There was no difference in first attempt success comparing the group of infants intubated with full compared with the no premedication group (aOR 1.7 (95% CI 0.8–3.3, p = 0.15).

Oxygen saturation and severe oxygen desaturation: The median pre-intubation oxygenation saturation was 100% (IQR 97,100) for all encounters. Severe oxygen desaturation episodes occurred in 47% of total encounters. There was no difference with respect to severe oxygen desaturation during intubation between groups (full vs. partial: P = 0.37, full vs. none: P = 0.23) (Table 2, Fig. 2). However, there was a significant difference in the multivariate analysis with nearly two times the occurrence of severe oxygen desaturation for intubations performed with partial premedication vs. no premedication (aOR 1.9 (95% CI 1.1–3.4), p = 0.03) (Fig. 3D).

In our single-center observational cohort study, we found that neonates receiving an opiate, vagolytic, and paralytic premedication before intubation were less likely to suffer an adverse TI associated event and had greater first attempt success compared with those receiving either a partial combination of premedication or no premedication. This improvement in TIAEs and first attempt success is especially relevant as neonatal TI remains a challenging technical skill, particularly for less experienced learners. In addition, the use of a full premedication may create a more controlled environment for intubation ensuring patient comfort while minimizing bradycardia and desaturation (3, 4, 6).

Despite recommendations in the neonatal intubation literature, much variability persists regarding premedication usage in the NICU. For example, Sarkar et al. surveyed NICU fellowship program directors and found that 44% of 78 programs responding used sedation for non-emergent TI while only 18% routinely used paralysis; 9 respondents co-administered atropine with opiate analgesia or sedative (e.g., benzodiazepine) and a paralytic (17). Similarly, Carbajal and colleagues reviewed eight studies, including four randomized trials, evaluating different premedication regimens for elective neonatal intubation, concluding that some combination of premedication should be used for all elective intubations, with the most studied regimen being the combination of fentanyl, atropine and a paralytic (5). The addition of atropine in this analysis adds a clinically relevant perspective surrounding the role of atropine in relation to clinically important adverse outcomes such as hypoxemia and bradycardia during tracheal intubation.

Our primary outcome was the incidence of adverse TIAEs between premedication groups. We found the group of infants intubated with full premedication to have significantly fewer adverse TI associated events even in the adjusted model compared to those who received both partial and no premedication. We did not find a difference in the incidence of adverse TIAEs comparing the partial premedication group with the no premedication group. This is in comparison to results in Ozawa et al. where they found a higher occurrence of adverse TIAEs for intubations in the sedation only group compared with no medication (4). Interestingly, similar to their study, we also identified higher odds of severe oxygen desaturation in the partial premedication groups compared to no premedication. These findings may be clinically relevant, particularly when premedication is considered for patients undergoing intubation for surfactant therapy with planned immediate extubation (INSURE) (21).

Patients intubated for INSURE remain at risk for adverse events associated with laryngoscopy and endotracheal tube placement. However, they are not good candidates for premedication with a paralytic as they must maintain spontaneous breathing immediately following extubation. While our study results showed no difference in TIAEs between the partial and no premedication groups there was significantly more hypoxemia during intubation with partial premedication. These results add to the literature evaluating the use of partial premedication for intubation. While we support use of premedication for INSURE to maintain patient comfort during awake intubation, we advise providers to use caution from the standpoint of adverse intubation events. (22, 23).

Our secondary outcomes included the change in heart rate during intubation and first attempt success between premedication groups. We found the partial and full premedication groups to have significantly less heart rate change during intubation than no premedication. This finding is in line with previous studies of intubation safety and adverse events (2, 6, 18, 24). Bradycardia during intubation may be due to vagal stimulation from laryngoscopy and endotracheal tube placement, as well as from hypoxemia (24); atropine mitigates this vagally induced bradycardia. Since atropine was used in nearly all intubations in the full premedication group and 83% of the partial premedication group, it was not surprising that we saw no difference in mild or severe bradycardia between full and partial premedication groups.

Even transient episodes of bradycardia may be clinically significant in that fluctuations in perfusion may be associated with changes in cerebral perfusion pressure and contribute to the development or worsening of intraventricular hemorrhage (6, 8, 10). Use of full premedication, including a paralytic, can potentially mitigate these changes in cerebral hemodynamics occurring during intubation, such as fluctuations in the partial pressure of carbon dioxide (pCO₂), bradycardia, and hypoxemia (10, 13). In our dataset, all infants with greater than 40% decrease from their highest recorded heart rate had a low heart rate during TI encounter of less than 100 bpm. Compared with partial and no premedication groups, we found significantly fewer infants in the full premedication group with this substantial decrease in heart rate (> 40% from highest recorded) during intubation. We did not investigate the timing nor incidence of intraventricular hemorrhage for infants in this cohort; however, these two clinically important outcomes should be rigorously explored in the context of transient yet large changes in vital signs during intubation particularly in very low birthweight infants.

We found higher first attempt success for neonates intubated with full premedication compared with partial premedication. Most infants in the partial premedication group received an opiate without paralytic, a scenario that may increase the likelihood of physiologic instability during laryngoscopy without the benefit of the paralytic to optimize the position and view of the glottic structures (4). Although there was a trend towards higher first attempt success between the full and no premedication groups, this was not statistically significant in this retrospective sample.

This study is limited by its data collection at a single center, retrospective approach, and relatively small number of participants. The intubating team collected data, and items such as the highest and lowest heart rate may have been recorded with variable accuracy. Using data from continuous electronic cardiorespiratory monitoring systems may reduce this potential for inconsistency in the future. Only the first TI course data were analyzed in this study which increases the risk of missing TIAEs occurring in subsequent TI courses within the same encounter. Future studies should employ techniques such as propensity score matching to reduce bias due to confounding, specifically in an observational cohort study with unbalanced treatment groups. Furthermore, as units move to utilize new tools and medication to improve the safety of neonatal intubation, it will be important to explore the role of practice changes to minimize variability in sampling.

We conclude that intubations with full premedication, including a vagolytic, opiate analgesic, and paralytic, are associated with fewer adverse TI events and increased first attempt success compared to intubations with a partial combination of premedication; even when adjusting for confounding variables. Compared to intubations without premedication, we found less change in heart rate during intubation with full premedication, a finding attributed to the addition of atropine to this analysis. The use of a regimen including vagolytic, analgesic, and paralytic should be considered as unit guidelines for neonatal intubation are developed.

Acknowledgements:

We would like to thank the pediatric residents, neonatal fellows, advance practice providers, and attending neonatologists at the University of Washington Medical Center, Montlake NICU, for their timely completion of the NEAR4NEOS data collection forms. We also extend thanks to Hayley Buffman and Elizabeth Foglia, MD, at the Children’s Hospital of Philadelphia for their commitment to neonatal intubation safety, creation, and maintenance of the NEAR4NEOS database.

Conflict of Interest:

The authors have no financial disclosures or conflicts of interest. NEAR4NEOS has been supported by NICHD HD089151. There was no direct funding for this analysis.

Author Contribution Statement:

SKN was responsible for study concept, data form auditing, extracting, and analyzing data, interpretation of results, and report writing. BKB was responsible for unit protocol changes, data form auditing, and report edits. RU contributed to the interpretation of results and provided feedback on the report. MMG guided with statistical analysis and presentation of data and provided feedback on the report. TS provided feedback on the report and AN and EF were responsible for generating the NEAR4NEOS centralized repository for neonatal intubation safety data and provided feedback on the report.

Sawyer T, Foglia E, Hatch LD, Moussa A, Ades A, Johnston L, et al. Improving neonatal intubation safety: A journey of a thousand miles. J Neonatal-Perinat Med. 2017;10(2):125–31.
Krick J, Gray M, Umoren R, Lee G, Sawyer T. Premedication with paralysis improves intubation success and decreases adverse events in very low birth weight infants: a prospective cohort study. J Perinatol [Internet]. 2018 Jun [cited 2020 Oct 16];38(6):681–6. Available from: http://www.nature.com/articles/s41372-018-0082-2
Foglia EE, Ades A, Napolitano N, Leffelman J, Nadkarni V, Nishisaki A. Factors Associated with Adverse Events during Tracheal Intubation in the NICU. Neonatology. 2015;108(1):23–9.
for the National Emergency Airway Registry for Neonates (NEAR4NEOS) Investigators, Ozawa Y, Ades A, Foglia EE, DeMeo S, Barry J, et al. Premedication with neuromuscular blockade and sedation during neonatal intubation is associated with fewer adverse events. J Perinatol [Internet]. 2019 Jun [cited 2021 Jan 5];39(6):848–56. Available from: http://www.nature.com/articles/s41372-019-0367-0
Carbajal R, Eble B, Anand KJS. Premedication for tracheal intubation in neonates: confusion or controversy? Semin Perinatol. 2007 Oct;31(5):309–17.
Roberts KD, Leone TA, Edwards WH, Rich WD, Finer NN. Premedication for nonemergent neonatal intubations: a randomized, controlled trial comparing atropine and fentanyl to atropine, fentanyl, and mivacurium. Pediatrics. 2006 Oct;118(4):1583–91.
Wallenstein MB, Birnie KL, Arain YH, Yang W, Yamada NK, Huffman LC, et al. Failed endotracheal intubation and adverse outcomes among extremely low birth weight infants. J Perinatol Off J Calif Perinat Assoc. 2016 Feb;36(2):112–5.
Dempsey EM, Al Hazzani F, Faucher D, Barrington KJ. Facilitation of neonatal endotracheal intubation with mivacurium and fentanyl in the neonatal intensive care unit. Arch Dis Child Fetal Neonatal Ed. 2006 Jul;91(4):F279-282.
Sauer CW, Kong JY, Vaucher YE, Finer N, Proudfoot JA, Boutin MA, et al. Intubation Attempts Increase the Risk for Severe Intraventricular Hemorrhage in Preterm Infants—A Retrospective Cohort Study. J Pediatr [Internet]. 2016 Oct [cited 2021 Feb 25];177:108–13. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022347616304176
Friesen RH, Honda AT, Thieme RE. Changes in anterior fontanel pressure in preterm neonates during tracheal intubation. Anesth Analg. 1987 Sep;66(9):874–8.
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 [Internet]. 2010 Mar 1 [cited 2020 Dec 19];125(3):608–15. Available from: http://pediatrics.aappublications.org/cgi/doi/10.1542/peds.2009-2863
Byrne E. Should premedication be used for semi-urgent or elective intubation in neonates? Arch Dis Child [Internet]. 2005 May 10 [cited 2020 Dec 23];91(1):79–83. Available from: https://adc.bmj.com/lookup/doi/10.1136/adc.2005.087635
Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010 Jan;67(1):1–8.
Glenn TJ, Grathwol MM, McClary JD, Wainwright RJ, Gorman SM, Rodriguez AM, et al. Decreasing Time from Decision to Intubation in Premedicated Neonates: A Quality Improvement Initiative. Pediatr Qual Saf [Internet]. 2019 Nov [cited 2021 Sep 30];4(6):e234. Available from: https://journals.lww.com/10.1097/pq9.0000000000000234
Hatch LD, Grubb PH, Lea AS, Walsh WF, Markham MH, Whitney GM, et al. Endotracheal Intubation in Neonates: A Prospective Study of Adverse Safety Events in 162 Infants. J Pediatr. 2016 Jan;168:62–66.e6.
Muniraman H, Yaari J, Hand I. Premedication Use Before Nonemergent Intubation in the Newborn Infant. Am J Perinatol [Internet]. 2015 Jan 21 [cited 2021 Jan 1];32(09):821–4. Available from: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0034-1543987
Sarkar S, Schumacher RE, Baumgart S, Donn SM. Are newborns receiving premedication before elective intubation? J Perinatol Off J Calif Perinat Assoc. 2006 May;26(5):286–9.
Lemyre B, Cheng R, Gaboury I. Atropine, fentanyl and succinylcholine for non-urgent intubations in newborns. Arch Dis Child Fetal Neonatal Ed. 2009 Nov;94(6):F439-442.
Nishisaki A, Turner DA, Brown CA, Walls RM, Nadkarni VM, National Emergency Airway Registry for Children (NEAR4KIDS), et al. A National Emergency Airway Registry for children: landscape of tracheal intubation in 15 PICUs. Crit Care Med. 2013 Mar;41(3):874–85.
Foglia EE, Ades A, Sawyer T, Glass KM, Singh N, Jung P, et al. Neonatal Intubation Practice and Outcomes: An International Registry Study. Pediatrics [Internet]. 2019 Jan [cited 2021 Jan 1];143(1):e20180902. Available from: http://pediatrics.aappublications.org/lookup/doi/10.1542/peds.2018-0902
Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003063.
Hodgson KA, Owen LS, Kamlin COF, Roberts CT, Newman SE, Francis KL, et al. Nasal High-Flow Therapy during Neonatal Endotracheal Intubation. N Engl J Med [Internet]. 2022 Apr 28 [cited 2022 May 5];386(17):1627–37. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2116735
Sk H, Saha B, Mukherjee S, Hazra A. Premedication with Fentanyl for Less Invasive Surfactant Application (LISA): A Randomized Controlled Trial. J Trop Pediatr. 2022 Feb 3;68(2):fmac019.
Marshall TA, Deeder R, Pai S, Berkowitz GP, Austin TL. Physiologic changes associated with endotracheal intubation in preterm infants. Crit Care Med. 1984 Jun;12(6):501–3.
Kelly MA, Finer NN. Nasotracheal intubation in the neonate: physiologic responses and effects of atropine and pancuronium. J Pediatr. 1984 Aug;105(2):303–9.
Barrington KJ, Finer NN, Etches PC. Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: a randomized, controlled trial. Crit Care Med. 1989 Dec;17(12):1293–6.
Haubner LY, Barry JS, Johnston LC, Soghier L, Tatum PM, Kessler D, et al. Neonatal intubation performance: room for improvement in tertiary neonatal intensive care units. Resuscitation. 2013 Oct;84(10):1359–64.

There is NO conflict of interest to disclose.

Download PDF

Editorial decision: revise
09 Dec, 2022
Review #1 received at journal
06 Dec, 2022
Review #2 received at journal
05 Dec, 2022
Reviewer #2 agreed at journal
21 Nov, 2022
Reviewer #1 agreed at journal
16 Nov, 2022
Reviewers invited by journal
11 Nov, 2022
Submission checks completed at journal
09 Nov, 2022
First submitted to journal
08 Nov, 2022
Editor assigned by journal
08 Nov, 2022

You are reading this latest preprint version

Association of full premedication on tracheal intubation outcomes in the neonatal intensive care unit: an observational cohort study

Status:

Version 1

Abstract

Figures

Introduction

Methods

Results

Primary outcome:

Secondary outcomes:

Discussion

Declarations

References

Additional Declarations

Status:

Version 1