In the last three decades, there has been a significant advance in the production of knowledge related to the assessment and management of neonatal pain. The finding that newborns (NB) can detect, process and react to algic1 stimulus and demonstrate permanent changes in immature brains in these patients2,3 have driven research aimed at understanding pain in this population, as well as strategies for its identification and management. In the past, invasive procedures and potentially painful, such as intratracheal intubation itself, were performed without any analgesia or sedation, which today is considered ethically unacceptable.

Intratracheal intubation is a stressful, painful, and potentially dangerous procedure that can lead to airway trauma, laryngospasm, bronchospasm, hemodynamic changes, and increased risk of intracranial hemorrhage. The practice of using premedications before intubation in adults and children, aiming to facilitate the procedure, and reduce pain, stress, and the deterioration of vital signs, is already well established. In the scope of newborns, there is no well-established practice of sedation and analgesia and few studies on the use of premedications.4

Among the main reasons for not using premedications for intratracheal intubation in the neonatal period are the short and long-term effects of these drugs, ranging from respiratory depression, hemodynamic instability, and even induction of neuroapoptosis. Therefore, on one hand, there are studies showing that the exposure to sedatives and analgesics in immature brains of this population is able to lead to important neurological changes, on the other hand, there is sufficient evidence showing the susceptibility to the pain of these patients and the negative neurological impact that these repeated experiences cause.

In this approach and aiming to contribute and add to the efforts to improve newborn care, this research aimed to assess the available evidence in the literature on the use of sedation and analgesia for intratracheal intubation of newborns.

This is a qualitative study, with data collected from primary and secondary sources, through a bibliographical survey of the integrative literature review type. The following steps of the integrative literature review method were followed: 1st) theme identification and selection of the hypothesis or research matter for the integrative review; 2nd) establishment of criteria for inclusion and exclusion of studies/sampling or literature search; 3rd) definition of the information to be extracted from the selected studies/categorization of the studies; 4th) evaluation of the studies included in the integrative review; 5th) interpretation of results; and 6th) presentation of the knowledge review/synthesis.5

Therefore, the guiding question of this research was: is sedation and/or analgesia used for intratracheal intubation of newborns? Then, a search for scientific articles on the subject was conducted in the period from March to October 2022.

The inclusion criteria for the studies were: articles in Portuguese, English and Spanish, published in the last ten years, in order to have more current evidence about the theme; complete texts that present in their discussions considerations on the use of sedation and/or analgesia for intubation of newborns admitted to neonatal intensive care units, indexed in the Pubmed, Lilacs, Medline, Scopus, and Scielo databases

The exclusion criteria were: articles repeatedly indexed in the databases and articles that did not meet the research objectives.

To perform the search, a combination of the following descriptors was used DeCS (Descritores em Ciência de Saúde - Health Science Descriptors) and MeSH (Medical Subject Heading): analgesia; newborn; and intubation, intratracheal. The boolean operator and other terms were used.

For the analysis and subsequent synthesis of the articles that met the inclusion criteria, a synoptic summary was used especially built for this purpose, which contemplated the following aspects: name of the research, year of publication, country, author, journal in which it was published, results/conclusion, and level of evidence.

The presentation of the results and discussion of the data obtained was descriptive, allowing the reader to evaluate the applicability and the positive impact on the quality of care of the newborn.

In this research the authors used, mainly, as a theoretical reference by Fritjof Capra, who through Systems Theory demonstrated that all problems are interconnected and interdependent, and this characteristic should be considered when thinking about an intervention.

After searching for the descriptors, 32 scientific articles were initially identified in the Pubmed database, and after applying the inclusion and exclusion criteria, three articles remained, which were read in full and included two in the review. In the Lilacs and Medline database via Biblioteca Virtual em Saúde (BVS) (Virtual Public health library), 20 articles were initially identified, and after applying inclusion and exclusion criteria, two articles remained (both from Medline), these were then read in full and included in this review. Initially, 65 articles were identified in the Scopus database, and after applying inclusion and deletion criteria, eleven articles remained, which were submitted to an exploratory reading of the abstracts, ten of which were eligible for full reading, and seven were included in this review. In the Scielo database, after searching for descriptors, no article was found. The steps of this process are represented in the PRISMA flow chart (Fig. 1).6

Figure 1.

Steps in the process of selecting the articles used for review.

(0.42MB).

Source: Page et al.6

The final sample of this review consisted of ten scientific articles. Table 1 shows a summary of the articles selected for this review.7-16

The studies were characterized according to their level of evidence, using the JBI (Instituto Joanna Briggs).

Among the articles included, narrative literature reviews and analytical observational studies without a control group predominate, with only one systematic review of quasi-experimental studies, and two quasi-experimental studies.

Table 2 presents the main medications used for sedation and analgesia in intratracheal intubation of neonates described in the selected articles.

For newborns, intubation is a common procedure in the neonatal ICU and also in the delivery rooms, but despite this, there is no well-established practice of sedation and analgesia and few studies on the use of premedications in this age group. This is confirmed by the small number of articles found on the subject in the various databases used in this research. There is evident little scientific production on the subject, and the absence of controlled and randomized clinical trials on the subject, which represent the highest degree of scientific evidence. The lack of randomization present in the clinical trials of the selected studies can generate biases and some limitations in the generalization of their conclusions.

In a recent review of evidence-based clinical guidelines, included in this study, there are strong recommendations for reducing neonatal stress and using non-pharmacological methods of pain control, combined with bolus analgesia of opioids before invasive procedures, as well as the use of premedications before intratracheal intubation. This recommendation is in line with the knowledge already built up on neonatal pain and also aims to make the procedure faster, less traumatic, and safer.

In the selected studies, there is a consensus recommending the use of premedications in non-emergency intratracheal intubations, which do not occur in emergency cases. This is reflected in the data obtained in a study conducted in France, where 100% of elective intubations were performed with analgesia and sedation versus 50% in emergencies and 90% in those considered semi-emergency. There is a trend described in the literature towards an increase in the use of analgesia, sedation, and protocols for intratracheal intubation over the years, which demonstrates a concern of the scientific community regarding the management of neonatal pain and its short and long-term effects.

Among the medications that could be used, one capable of producing analgesia and sedation quickly was sought, and that had a short half-life and no major side effects. Regarding to this, the authors have two prospective studies. One of the clinical trial dosage types, is where the author studies the use of propofol for the intubation of newborns and investigates the dose capable of producing analgesia and sedation without side effects. In this study, it was found that high doses were needed to produce good sedation and analgesia, which led to hypotension in almost 60% of the patients, making its use impractical, in view of the wide variety of responses in the different gestational ages of newborns. The other is a study on the feasibility and efficacy of the use of ketamine as an analgesic for intubation in the delivery room. Both studies are characterized by the lack of randomization of patients submitted or not to drug intervention, leaving this decision at the discretion of the attending physician, which can generate biases.

The remaining articles that make up this review are descriptive retrospective studies and reviews. There are several possible combinations of medications that are used according to the clinical situations of each patient, but they mostly consist of an analgesic, a sedative, a vagolytic, and a muscle relaxant.

As for the most used medications: the recommendation of not using midazolam as a sedative in premature infants (due to its hypotensive effect) is maintained; there is a strong tendency to use remifentanil instead of morphine for analgesia, in view of its more favorable pharmacokinetics; the use of muscle relaxants is restricted to professionals with more experience in the procedure; atropine can be used to reduce bradycardia induced by intubation; propofol is a possibility in full-term and near-term newborns, and in patients, without venous access, there is the possibility of using intranasal midazolam and fentanyl.

Despite the INSURE technique, often used in neonatal ICU, where the patient is intubated only to receive surfactant replacement and then quickly extubated, there is a need to maintain a good respiratory drive after the procedure, this has long led to resistance to the use of analgesia and sedation, due to fear of drug-induced respiratory depression. In the current literature, there is a preference in these cases for the use of remifentanil as a premedication, followed, if necessary, by reversal with naloxone, with excellent results.

Pain in the neonatal period and its deleterious effects should not be neglected, it should always be considered and treated. It is ethically unacceptable, in view of the already demonstrated ability of the NB to feel pain, to perform any procedure considered potentially painful in adults or children, without the use of analgesia. More studies on the best combinations of medications are needed, including investigations on efficacy and safety. Each neonatal ICU should develop its own premedication protocol in conjunction with its neonatal pain identification and management protocol.