Dear Editor:

A recent advance in premedicating infants requiring intubation has gained wide acceptance for humanitarian and physiological reasons.[1] The use of muscle relaxation to facilitate intubation is quite separate from sedation providing analgesia, amnesia and lack of awareness.

Practice is variable with little evidence-based guidance to suitable drugs. Clinical Governance dictates continuing audit of any such practice supported with written guidelines. We advocate a minimum monitoring policy (Saturation, Pulse, Non-Invasive Blood Pressure and Respiratory rate) and the presence of at least two skilled operators, one of which should be an experienced specialist registrar or consultant, when using neuromuscular blockade. This exercise is reserved for elective intubations and tube changes but not for use in resuscitation on the labour suite.

Recent reports to the CSM (Committee for the Safety of Medicines) via the UK Yellow Card Scheme of mortality associated with premedication using atracurium (dose 500 mcg/kg) and diamorphine (dose 50 mcg/kg) in three premature infants (24, 26 and 26 weeks' gestation) have attributed the problem mainly to using atracurium, which we consider debatable (Nicholas Rutter, Nottingham; Personal Communication). In addition, neuromuscular blockade should be unnecessary in pre-term infants.

Diamorphine is a prodrug that is metabolised to active 6-0-acetylmorphine and then to morphine. It has faster CNS penetration than morphine due to increased lipid solubility but its side effects are similar. Bradycardia of vagal origin (in combination with laryngoscopy) and decreased sympathetic response can cause a fall in cardiac output. Both morphine and atracurium cause histamine release that can precipitate bronchospasm and a fall in systemic vascular resistance (SVR).

Atracurium is a non-depolarising muscle relaxant that is slow onset and long acting. It provides intubating conditions within 90 seconds (dose 300-600 mcg/kg) and has a recovery index of 16 minutes (adult data). Premature infants have a small functional residual capacity (FRC) particularly when paralysed. A rapid fall in alveolar oxygen in an already under-ventilated infant may lead to pulmonary hypertension and increase V/Q mismatch. Consequently, mask ventilation or tube placement becomes necessary before the 90 seconds, which may not be long enough to reach therapeutic levels. Patients receiving a long acting muscle relaxant that cannot be ventilated for whatever reason will not start any independent respiratory effort for at least 16 minutes!

Our guidelines propose using fentanyl (dose 2 mcg/kg), which does not cause histamine release, so there is no bronchospasm. Cardiac output, systemic vascular resistance, pulmonary vascular resistance, and pulmonary artery occlusion pressure are preserved. High doses (10-15 mcg/kg) can lead to vagal bradycardias or chest wall rigidity. Where a muscle relaxant is indicated, we suggest suxamethonium (dose 1 mg/kg) which is to be preceded with atropine.

References
(1) Whyte S, Birrell G, Wyllie J. Premedication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82:F38-F41.

Dear Editor

With great interest we read the paper by Whyte et al regarding the practice of premedication before intubation in UK neonatal units.[1] Their finding that only 37% of the units gave any sedation before intubation is worrysome in view of the known physiologic responses to awake intubation.[2-4] However, one potential bias in their study design was not discussed.

Since the information regarding this subject was derived from telephonic interviews with the sister in charge of the unit the results might merely reflect the policy of the unit as perceived by this person and not the practice of the individual neonatologist performing or supervising the intubation. Whether this would result in underscoring or overscoring on the subject remains to be answered.

In our experience sustantial interindividual variation exists among neonatologists in the use of premedication before intubation of neonates. In March of 1999 we performed a written survey among all neonatologists and fellows working on each of the 10 neonatal intensive care units (NICUs) in The Netherlands. The response rate was 77/87 (89%). Of the respondents, 58 (76%) always gave some form of analgesia or sedation prior to intubation, 13 (16%) only sometimes gave premedication, whereas 6 (8%) never gave premedication. Of those who always gave premedication 33 (57%) always combined the use of sedation with a muscle relaxant. Only 15 (17%) used a written protocol for premedication.

Similar to Whyte’s results great variation existed with regard to the choice and dose regimen of the premedication. Morphine was the most widely used opioid, followed by fentanyl and pethidine. Midazolam was the most popular sedative. On a few occasions, ethomidate was mentioned as anaesthetic drug. Atropine was sometimes used in patients with proven rapid onset of reflex bradycardia. From these results it appears that premedication before intubation of neonates is the rule rather than the exception in the NICU environment in The Netherlands, although overscoring cannot be ruled out. When analysed on a per NICU basis it was obvious that a great intra-NICU variation in the practice of premedication exists.

Our results closely resemble those of a recent survey among Canadian neonatologists which showed that in approximately 75% of cases some premedication before intubation is used in Canadian NICUs.[5] It would be interesting to see the results of a survey among neonatologists in the UK.

The known physiological responses to awake intubation include bradycardia, hypertension, hypoxemia, laryngospasm and increased intracranial pressure (2-4). Moreover, awake intubation requires more attempts, is more time-consuming and is accompanied with more mucosal damage than premedicated intubation.[6] Optimal prevention of these adverse effects probably requires the combination of a vagolytic, an opioid and a muscle relaxant.[7] Therefore, in our institution the combination of atropine (0.1 mg), morphine (0.05-0.1 mg/kg) and vecuroniumbromide (0.05-0.1 mg/kg) is routinely applied with great satisfaction. We fully agree with Whyte et al[1] that there is now sufficient evidence to support the routine practice of premedication for elective intubation of neonates. Indeed, more research is needed to investigate the optimal drug and dose regimen.

REFERENCES

1. Whyte S, Birrell G, Wyllie J: Premedication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82:F38-F41.

2. Marshall TA, Deeder R, Pai S, Berkowitz GP, Austin TL: Physiologic changes associated with endotracheal intubation in preterm infants. Crit Care Med 1984; 12(6):501-3.

3. Kelly MA, Finer NN: Nasotracheal intubation in the neonate: Physiologic responses and effects of atropine and pancuronium. J of Pediatrics 1984;105:303-9.

4. Friesen RH, Honda AT, Thieme RE: Changes in anterior fontanel pressure in preterm neonates during tracheal intubation. Anesth Analg 1987;66:874- 8.

5. Vogel S, Gibbins S, Simmons B, Shah V: Premedication for endotracheal intubation (EI) in neonates: A Canadian Perspective. Pediatric Research 2000;47(4):438A.

6. Oei J, Hari R, Lui K: Suxamethonium, atropine and morphine as induction for neonatal nasotracheal intubation: A randomised controlled trial. Pediatric Research 2000;47(4):421A.

7. Barrington KJ, Byrne PJ: Premedication for neonatal intubation. Am J of Perinatol 1998;15(4):213-6.

Harry Molendijk, MD, Neonatologist

Anneke Jaarsma, MD, Neonatologist

Beatrix Children’s Hospital
Department of Pediatrics, Subdivision of Neonatology
University Hospital Groningen, P.O. Box 30001
9700 RB Groningen, The Netherlands

Editor,

Neonates are exposed to many procedures, including intubation, IV access, central line placement, chest tube insertion, lumber puncture, catheterisation, suprapubic aspiration etc. These procedures are associated with pain and stress. No clear guidelines are available for alleviating the distress by premedication before such procedures. Researchers are looking for methods to minimise the pain and distress in neonates during these procedures.

Examples include the use of thiopental as premedication before intubation,(1) local anaesthetics before heel prick,(2) and response to cutaneous stimulus.(3) In the recent issue of the journal three articles (1,3,4) were on the issue of premedication before procedures in neonates. However, there is no consensus regarding the policy and protocol for use of premedication before procedures in neonates. The issue of is not so simple. In the present era of evidence medicine, more randomised control trials are needed so that the experts can reach to a consensus. The questions need research are: the type of drug (analgesic, sedative or anaesthetics), the mode of administration (IM, IV, ET) and the dose to be used.

Yours sincerely,

Dr.Shabih Manzar,FAAP
Assistant Professor, Department of Pediatrics
King Fahd University Hospital
P.O.Box 40211, Al-Khobar 31952
Saudi Arabia

References:

1. 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-F37

2. Barker DP, Rutter N. Lignocaine ointment and anaesthesia in preterm infants. Arch Dis Child Fetal Neonatal Ed 1995;72:F203-4

3. Jain A, Rutter N. Local anaesthetic effect of topical amethocaine gel in neonates: randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2000;82:F42-F45

4. Whyte S, Birrell G, Whyllie J. Premedication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82:F38-F41

The paper by Bhutada et al (1) adds to the growing body of evidence that premedication for tracheal intubation in neonates both improves physiological stability and makes the procedure easier to perform. The results of the telephone survey of premedication use in UK neonatal units by Whyte et al (2) helps to define current practice. In a similar study, we recently tried to define the routine use of premedication for tracheal intubation in term and pre-term neonates in Australia and the UK - allowing comparisons to be made.

A survey was conducted of practice in Australian level 3 units (21) and UK units with 6 or more intensive care cots (52). The format was a semi-structured telephone interview of the nurse in charge of the shift when the call was made. All interviews were conducted by one of two of the authors (SWH and JB) in September 1999.

There was a 100% response rate. Results were:

	United Kingdom		Australia
	Term	Pre-term	Term	Pre-term
Routine premedication (%)	22(42)	18(34)	15(71)	14(67)
Opiate	13	11	2	4
Benzodiazepine (BDZ)	1	0	2	1
Opiate + BDZ	1	1	0	0
Opiate + muscle relaxant +/- atropine	6	6	11	9
BDZ + muscle relaxant +/- atropine	1	0	0	0

Seven different combinations of premedication drugs were in routine use in Australia compared to 14 different combinations in the UK.

In Australian units, the routine administration of premedication for non-emergency tracheal intubation of term and pre-term neonates is common practice and there is some uniformity in the combinations of drugs used. In contrast this practice is less common in the UK and there is more diversity of prescribing. In both countries premedication was more commonly used for term neonates. This difference in practice may reflect the fact that larger babies are more likely to struggle when intubated - making the procedure more technically demanding.

We agree with Whyte et al that there is a strong evidence-based argument for premedication for tracheal intubation in neonates to be routine. Our work brings added clarity to the existing picture and confirms that there is little consensus as to the best combination of drugs to use. Further work to define best practice is urgently required.

1 Bhutada A, Sahani R, Rastogi S, Wung J-T. Randomised controlled trial of thiopental for intubation in neonates. Arch Dis Child Fetal Neonatal Ed 2000;82:F34-F37.

2 Whyte S, Birrell G, Wyllie J. Premedication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82:F38-F41.