Year : 2012 | Volume
| Issue : 4 | Page : 385-392
Premedication for neonatal intubation: Current practice in Saudi Arabia
Rafat Mosalli1, Lana Shaiba2, Khalid AlFaleh2, Bosco Paes3
1 Department of Pediatrics, Umm Al Qura University, Mecca; International Medical Center, Jeddah, Saudi Arabia
2 Department of Pediatrics (Neonatal Division), King Saud University, Riyadh, Saudi Arabia
3 McMaster University, Hamilton, Ontario, Canada
Department of Pediatrics, Umm Al Qura University, PO Box 7607, Mecca
Source of Support: None, Conflict of Interest: None
|Date of Web Publication||10-Jan-2013|
Background: Despite strong evidence of the benefits of rapid sequence intubation in neonates, it is still infrequently utilized in neonatal intensive care units (NICU), contributing to avoidable pain and secondary procedure-related physiological disturbances. Objectives: The primary objective of this cross-sectional survey was to assess the practice of premedication and regimens commonly used before elective endotracheal intubation in NICUs in Saudi Arabia. The secondary aim was to explore neonatal physicians' attitudes regarding this intervention in institutions across Saudi Arabia. Methods: A web-based, structured questionnaire was distributed by the Department of Pediatrics, Umm Al Qura University, Mecca, to neonatal physicians and consultants of 10 NICUs across the country by E-mail. Responses were tabulated and descriptive statistics were conducted on the variables extracted. Results: 85% responded to the survey. Although 70% believed it was essential to routinely use premedication for all elective intubations, only 41% implemented this strategy. 60% cited fear of potential side effects for avoiding premedication and 40% indicated that the procedure could be executed more rapidly without drug therapy. Treatment regimens varied widely among respondents. Conclusion: Rates of premedication use prior to non-emergent neonatal intubation are suboptimal. Flawed information and lack of unified unit policies hampered effective implementation. Evidence-based guidelines may influence country-wide adoption of this practice.
Keywords: Endotracheal intubation, neonate, premedication, sedation
|How to cite this article:|
Mosalli R, Shaiba L, AlFaleh K, Paes B. Premedication for neonatal intubation: Current practice in Saudi Arabia. Saudi J Anaesth 2012;6:385-92
|How to cite this URL:|
Mosalli R, Shaiba L, AlFaleh K, Paes B. Premedication for neonatal intubation: Current practice in Saudi Arabia. Saudi J Anaesth [serial online] 2012 [cited 2022 Jun 25];6:385-92. Available from: https://www.saudija.org/text.asp?2012/6/4/385/105878
| Introduction|| |
Increasing evidence suggests that intubation of neonates, particularly in an awake state, is an invasive and potentially distressing procedure associated with a variety of undesirable hemodynamic complications such as hypoxemia, bradycardia, hypertension, and intracranial hypertension. ,,,, In premature infants, it could result in intraventricular hemorrhage with potential long-term sequelae. , Although premedication for endotracheal intubation may lower the incidence of side effects, it is currently underused due to lack of adequate training or standardization among neonatal units. The implementation of an effective premedication protocol and policy for nonemergent intubation may minimize intubation-related injuries and the number of unsuccessful intubations and may also improve physiological stability in the newborn. ,
| Aims and Objectives|| |
The primary objective of this cross-sectional survey was to assess the practice of premedication and regimens commonly used before elective endotracheal intubation. The secondary aim was to explore neonatal physicians' attitudes regarding this intervention in institutions across Saudi Arabia prior to the development of evidence-based recommendations.
| Methods|| |
An 8-item web-based structured questionnaire [Table 1] was developed using pertinent items on the topic from a literature review ,, and those of local relevance. The content of the survey items were reviewed for clinical sensibility and clarity and initially agreed upon by two neonatologists (RM and KA-F) and subsequently the neonatologists in their respective centers. It was then distributed, in a single-stage, non-randomly via E-mail, to neonatal physicians and consultants across 10 largest academic, tertiary, neonatal intensive care units (NICU) in Saudi Arabia. The questionnaire was designed to elicit responses regarding knowledge, attitudes, and the use of premedication for elective intubation, existing guidelines, or policies for the procedure with appropriate monitoring and treatment of potential side-effects, and the medication sequence employed. Data were collected using the online survey engine (available at www.surveymonkey.com) and was analyzed using the corresponding survey software. The questions were brief, each addressing a single issue and the majority evoked a simple "yes" or "no" response to the closed ended questions. The questionnaire and the survey protocol were forwarded to the Ethics Review Board at King Khalid University Hospital and consent for participation in the study was exempted.
Descriptive, quantitative, outcomes were sought to investigate main reasons for withholding premedication prior to non-emergent intubation. All frequency and cross-tabulation analyses were performed using the statistical software package IBM SPSS; 19.0, 2010. Descriptive statistics were utilized to analyze the variables and are reported as percentages in the respective tables.
| Results|| |
Of the 80 neonatal clinicians contacted by E-mail, 68 (85%) responded to the survey [Table 2]. ,,,,, The majority of the respondents were consultants (75%), whereas 25% were full-time physicians practicing in tertiary level NICUs.
|Table 2: Summary of the surveys on premedication for elective intubation|
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Of the respondents, only 28 (41%) were using premedication prior to intubation, but all respondents were in agreement that neonates feel pain during the intubation procedure. Forty-eight (70%) of the 68 surveyed individuals believe it is essential to use premedication as a standard protocol for all elective intubations.
Most clinicians who did not offer premedication prior to elective intubation in their practice had concerns regarding potential side effects (60%) and believed that intubation was quicker without premedication (40%) and raised lack of proper training (5%) as a reason for withholding or withdrawing the routine use of premedication.
Only 18/68 (26%) respondents indicated the availability of a written policy/protocol in their units and of those 22% had guidelines for drug reversal.
The most common medications administered were midazolam (40%), fentanyl (36%), and morphine (30%): 30 respondents used these agents for premedication, either alone or in combination. Nine (30%) of those who utilized premedication prior to intubations administered neuromuscular blockade in the form of suxamethonium or rocuronium. Only seven of 30 individuals (23%) reported the combined use of atropine, sedation, and neuromuscular blockade to facilitate intubation.
| Discussion|| |
Although there is growing and compelling evidence that premedication for non-urgent intubations in neonates is safer, quicker, and more effective than awake intubations, ,, this procedure is not performed routinely for all neonates. ,,,
Recently, the American Academy of Pediatrics (AAP) guidelines for rapid sequence intubation (RSI) in neonates provided standardization regarding the use of premedication for elective or semi-elective intubation.  Our study indicates that most elective intubations are performed in the NICU as awake intubations (without the use of sedatives, analgesia, or muscle relaxant) despite the cumulative evidence of the benefits of premedication. Data from published surveys compared to our results are shown in [Table 2]. In our survey, only 41% of the respondents routinely use medication prior to intubation [Table 2]. Our findings for under-use of premedication are consistent with reports from other countries. ,,,,
Awake intubation is associated with severe distress and acute changes in vital signs with accompanying heart rate variability, elevated blood pressure, oxygen desaturation, and intracranial hypertension. ,, In addition, prolongation of the procedure, even with a successful first attempt, the requirement for multiple attempts, and the potential for supraglottic injury may further adversely impact the preprocedure normalcy of a newborn's clinical status. ,,, [Table 3] ,,,,,,, summarizes randomized controlled trials detailing the effects of non-medication-assisted neonatal intubation compared to various premedications in the treatment arms of the respective studies.
The present study identifies some likely reasons for not offering premedication to neonates. These may include concerns over adverse effects and lack of familiarity regarding the benefits of premedication. This is consistent, for the most part, with the barriers reported by Ziegler  but was not evident in a large multicenter observational study by Simon et al.  Strategies to overcome misconceptions about the routine utilization of premedication should address both personal and knowledge-deficient barriers through continuous education, identify appropriate treatment regimens (RSI medications) together with raising awareness of potential side effects and specific methods of drug reversal. ,, Tracheal intubation without the use of analgesia or sedation should be performed only for urgent or life-threatening situations such as resuscitations in the delivery room or sudden, unanticipated cardio-respiratory decompensation in the NICU setting. 
|Table 3: Randomized controlled trials detailing the effects of non-medication-assisted neonatal intubation|
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The results reported indicate considerable variation in drugs used for premedication. Sedatives (mostly midazolam) are being increasingly used without an analgesic. Midazolam should not be administered alone without an analgesic because it causes serious complications which include hypotension, compromised cardiac output, and cerebral blood flow velocity. ,, In an animal model, rabbits premedicated with fentanyl followed by induction of anesthesia with midazolam resulted in hypotension with reduced quality of recovery.  Similar reports of hypotension with the combined use of fentanyl and midazolam have been documented during electrophysiological procedures,  and sedation and anesthesia. , Moreover, in preterm babies (<33 weeks gestational age), midazolam is associated with adverse neurological events. , Only 23% reported using atropine and only 30% of the respondents use a muscle relaxant. In addition, our study highlighted a lack of consensus about the best combination and drug sequences for RSI. Although there are a variety of premedication protocols reported in the literature for elective neonatal endotracheal intubation, there is no clear agreement about the best combination or sequence of drug administration.  In general, premedication drugs should have a rapid onset and short duration of action and comprise anticholinergic agents to reduce the incidence of bradycardia. A reasonable regimen that is widely utilized involves a vagolytic agent such as atropine, an opioid (fentanyl or remifentanyl) to ameliorate intubation-induced pain and hemodynamic instability, followed by a paralyzing agent (suxamethonium or rocuronium) to facilitate neuromuscular blockade. ,,, Of note, although the efficacy of suxamethonium as a short-duration muscle relaxant has been proven in randomized clinical trials, ,, its association with rare adverse events such as hyperkalemia, malignant hyperthermia, cardiac arrhythmias, and rhabdomyolysis make it a less preferred agent compared to rocuronium and vecuronium.  A proposed algorithm for premedication is shown in [Figure 1]. ,,,,
|Figure 1: Algorithm for premedication for elective endotracheal intubation in neonates|
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It is evident from this survey that the majority of neonatal units lack a detailed written policy for routine premedication which encompasses a guideline for drug dosage, appropriate drug combinations, a specific sequence for drug administration, and recommendations for drug reversal of unanticipated side effects. 
The policy should encourage the use of pre-prepared syringes to reduce errors and time consumed for drug preparation.  Such policies would standardize the approach to elective intubation and reduce variability in practice among neonatal practitioners in the same unit and across units.
Documentation must become a prerequisite for the procedure and be strongly enforced in the respective institutions. A structured outline must minimally include route of intubation (oral/nasal), endotracheal tube size, premedication drug doses, time of administration, vital signs before and after the onset of the procedure, and side effects with appropriate corrective treatment recorded. Neonatal teams involved in the intubation should communicate as the medications are given. They should comprise one recorder to document events occurring, a single individual allocated to medication delivery who should also be ready to provide drug antidotes if required, and a skilled practitioner who should be dedicated for airway management (use of bag-mask ventilation/laryngeal mask or supraglottic backup airway, laryngoscopy, and intubation).  Antidotes such as naloxone, an opioid antagonist for the reversal of opioid-induced respiratory depression, flumazenil to counteract the effect of benzodiazepines, and neostigmine with atropine to combat the adverse effects of rocuronium should be immediately available. It is important to recognize that there is no reversal agent for suxamethonium and the infant should be ventilated until the short-duration depolarizing action terminates.
To the best of our knowledge, this is one of the few well-conducted surveys on premedication in the region and one of the few studies that has evaluated attitudes and actual practice of neonatal physicians, in an attempt to identify possible barriers to premedication use. The limitations of this study include the use of a self-developed instrument that was founded on reliable scientific literature but not previously validated, the absence of pilot testing of the survey, and a possible response selection bias despite the 85% response rate. The positive assets are an assessment of physician attitudes and barriers which were coupled in the same survey and an examination of drug reversal policies [Table 2]. Hopefully, our data will prove valuable in establishing regional multidisciplinary, educational strategies in order to streamline an evidence-based approach to premedication and ensure both changes in attitude and regional clinical practice. The ultimate goals perhaps will be best achieved over time as was evident in the surveys conducted across Britain. ,
| Conclusion|| |
Rates of premedication prior to non-emergent intubation in neonates are suboptimal in Saudi Arabia but the findings are not strikingly dissimilar to the other published surveys. Flawed information and lack of unified unit policy have impeded effective implementation. The findings may also have implications for pediatricians practicing in advanced level 2 nurseries where the approach to intubation may need standardization. Development of evidence-based guidelines in the format of a position statement, especially if steered through the Saudi Neonatal Society and other similar international pediatric advisory bodies, might garner better support for the widespread utilization of premedication for elective intubation in countries worldwide.
| References|| |
|1.||Millar C, Bissonnette B. Awake intubation increases intracranial pressure without affecting cerebral blood flow velocity in infants. Can J Anaesth 1994;41:281-7. |
|2.||Pokela ML, Koivisto M. Physiological changes, plasma beta-endorphin and cortisol responses to tracheal intubation in neonates. Acta Paediatr 1994;83:151-6. |
|3.||Marshall TA, Deeder R, Pai S, Berkowitz GP, Austin TL. Physiologic changes associated with endotracheal intubation in preterm infants. Crit Care Med 1984;12:501-3. |
|4.||Raju TN, Vidyasagar D, Torres C, Grundy D, Bennett EJ. Intracranial pressure during intubation and anesthesia in infants. J Pediatr 1980;96:860-2. |
|5.||Stow PJ, McLeod ME, Burrows FA, Creighton RE. Anterior fontanelle pressure responses to tracheal intubation in the awake and anaesthetized infant. Br J Anaesth 1988;60:167-70. |
|6.||Friesen RH, Handa AT, Thieme RE. Changes in anterior fontanel pressure in preterm neonates during tracheal intubation. Anesth Analg 1987;66:874-8. |
|7.||Durand M, Sangha B, Cabal LA, Hoppenbrouwers T, Hodgman JE. Cardiopulmonary and intracranial pressure changes related to endotracheal suctioning in preterm infants. Crit Care Med 1989;17:506-10. |
|8.||VanLooy JW, Schumacher RE, Bhatt-Mehta V. Efficacy of a premedication algorithm for nonemergent intubation in a neonatal intensive care unit. Ann Pharmacother 2008;42:947-55. |
|9.||Kumar P, Denson SE, Mancuso TJ. Premedication for nonemergency endotracheal intubation in the neonate. Pediatrics 2010;125:608-15. |
|10.||Simon L, Trifa M, Mokhtari M, Hamza J, Treluyer JM. Premedication for tracheal intubation: A prospective survey in 75 neonatal and pediatric intensive care units. Crit Care Med 2004;32:565-8. |
|11.||Whyte S, Birrell G, Wyllie J. Premedication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82:F38-41. |
|12.||Sarkar S, Schumacher RE, Baumgart S, Donn SM. Are newborns receiving premedication before elective intubation. J Perinatol 2006;26:286-9. |
|13.||Ziegler JW, Todres ID. Intubation of newborns. Am J Dis Child 1992;146:147-9. |
|14.||Vogel S, Gibbins S, Simmons B, Shah V. Premedication for endotracheal intubation (EI) in neonates: A Canadian perspective. Pediatr Res 2000;47:438A. |
|15.||Kelleher J, Mallya P, Wyllie J. Premedication before intubation in UK neonatal units: A decade of change? Arch Dis Child Fetal Neonatal Ed 2009;94:F332-5. |
|16.||Chaudhary R, Chonat S, Gowda H, Clarke P, Curley A. Use of premedication for intubation in tertiary neonatal units in the United Kingdom. Paediatr Anaesth 2009;19:653-8. |
|17.||Barrington K. Premedication for endotracheal intubation in the neonate. Paediatr Child Health 2011;16:159-71. |
|18.||Duncan HP, Zurich NJ, Wolf AR. Should we reconsider awake neonatal intubation? A review of the evidence and management strategies. Paediatr Anaesth 2001;11:135-45. |
|19.||Oei J, Hari R, Butha T, Lui K. Facilitation of neonatal nasotracheal intubation with premedication: A randomized controlled trial. J Paediatr Child Health 2002;38:146-50. |
|20.||Shah V, Ohlsson A. The effectiveness of premedication for endotracheal intubation in mechanically ventilated neonates. A systematic review. Clin Perinatol 2002;29:535-54. |
|21.||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;91:F279-82. |
|22.||Pereira e Silva Y, Gomez RS, Marcatto Jde O, Maximo TA, Barbosa RF, Simões e Silva AC. Morphine versus remifentanil for intubating preterm neonates. Arch Dis Child Fetal Neonatal Ed 2007;92:F293-4. |
|23.||Ghanta S, Abdel-Latif ME, Lui K, Ravindranathan H, Awad J, Oei J. Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: A randomized controlled trial. Pediatrics 2007;119:e1248-55. |
|24.||Kelly MA, Finer NN. Nasotracheal intubation in the neonate: Physiologic responses and effects of atropine and pancuronium. J Pediatr 1984;105:303-9. |
|25.||Hassid S, Nicaise C, Michel F, Vialet R, Thomachot L, Lagier P, et al. Randomized controlled trial of sevoflurane for intubation in neonates. Paediatr Anaesth 2007;17:1053-8. |
|26.||Lemyre B, Doucette J, Kalyn A, Gray S, Marrin ML. Morphine for elective endotracheal intubation in neonates: A randomized trial [ISRCTN43546373]. BMC Pediatr 2004;4:20. |
|27.||Bhutada A, Sahni R, Rastogi S, Wung JT. Randomised controlled trial of thiopental for intubation in neonates. Arch Dis Child Fetal Neonatal Ed 2000;82:F34-7. |
|28.||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;17:1293-6. |
|29.||Anand KJ. International Evidence-Based Group for Neonatal Pain. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001;155:173-80. |
|30.||Shekerdemian L, Bush A, Redington A. Cardiovascular effects of intravenous midazolam after open heart surgery. Arch Dis Child 1997;76:57-61. |
|31.||Harte GJ, Gray PH, Lee TC, Steer PA, Charles BG. Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates. J Paediatr Child Health 1997;33:335-8. |
|32.||Jacqz-Aigrain E, Daoud P, Burtin R, Desplanques L, Beaufils F. Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies. Lancet 1994;344:646-50. |
|33.||Martinez MA, Murison PJ, Love E. Induction of anaesthesia with either midazolam or propofol in rabbits premedicated with fentanyl/fluanisone. Vet Rec 2009;164:803-6. |
|34.||Pachulski RT, Adkins DC, Mirza H. Conscious sedation with intermittent midazolam and fentanyl in electrophysiology procedures. J Interv Cardiol 2001;14:143-6. |
|35.||Campbell SG, Magee KD, Kovacs GJ, Petrie DA, Tallon JM, McKinley R, et al. Procedural sedation and analgesia in a Canadian adult tertiary care emergency department: A case series. CJEM 2006;8:85-93. |
|36.||Neidhart P, Burgener MC, Schwieger I, Suter PM. Chest wall rigidity during fentanyl- and midazolam-fentanyl induction: Ventilatory and hemodynamic effects. Acta Anaesthesiol Scand 1989;33:1-5. |
|37.||Anand KJ, Barton BA, McIntosh N, Lagercrantz H, Pelausa E, Young TE, et al. Analgesia and sedation in preterm neonates who require ventilatory support: Results from the NOPAIN trial. Arch Pediatr Adolesc Med 1999;153:331-8. |
|38.||Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev 2003;6:CD002052. |
|39.||Lemyre B, Cheng R, Gaboury I. Atropine, fentanyl, and succinylcholine for non-urgent intubations in newborns. Arch Dis Child Fetal Neonatal Ed 2009;94:F439-42. |
|40.||Feltman DM, Weiss MG, Nicoski P, Sinacore J. Rocuronium for nonemergent intubation of term and preterm infants. J Perinatol 2011;31:38-43. |
|41.||Rapp HJ, Altenmueller CA, Waschke C. Neuromuscular recovery following rocuronium bromide single dose in infants. Paediatr Anaesth 2004;14:329-35. |
|42.||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;118:1583-91. |
[Table 1], [Table 2], [Table 3]
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