Table 4

 Premedication for semi-urgent intubation

Citation, countryStudy groupStudy type (level of evidence)OutcomeKey resultsStudy weaknesses
Lemyre et al (2004), Canada134 infants randomly assigned to receive morphine 0.2 mg/kg IV or placebo (0.9% sodium chloride), for elective intubationDouble blind randomised control trial. (level 1b)Duration of severe hypoxaemiaNo significant differenceDifferent levels of experience of people performing the intubations (help called). Variations in time of preoxygenation and hand ventilation
Duration of hypoxaemiaNo significant difference
Duration of procedureNo significant difference
Max increase in mean blood pressureNo significant difference
Number of attemptsNo significant difference
Number where intubation was achieved at first attemptNo significant difference
Number where intubation needed a rescue intubatorNo significant difference
Bradycardia during procedureNo significant difference
Oei et al (2002), Australia220 infants randomised to awake intubation or premedication with morphine 100 μg/kg, atropine 10 μg/kg and suxamethonium 1 mg/kgNon-blinded randomised control trial (level 1b)Heart rateSignificantly greater drop in awake infants. (68±47 bpm v 29±39 bpm; p = 0.017)Lack of blinding. Small sample size. Groups not completely matched. Two infants had to be moved from the awake group to the premedicated group. In 8 of the intubation attempts the awake infants lowest heart rate and oxygen saturation could not be recorded
Oxygen saturationNo significant difference
Total time taken to complete intubationSignificantly shorter in premedicated infants (median 60.5 seconds v 595 seconds; p =  0.016)
Number of attempts at intubationMore than twice as many attempts in the awake group (p = 0.01)
Bhutada et al (2000), America330 neonates weighing over 2 kg at birth and requiring semi-elective or elective intubation. Randomised into thiopental 6 mg/kg or the equivalent volume of physiological salineRandomised, placebo controlled trial (level 1b)Heart rateSignificant changes (mean (SE) −0.5 [4.4] v 12.0 [3.2] bpm; p<0.03)Lack of blinding. Small sample size
Heart rate variabilitySignificantly less variable in study group (mean (SE) −2.0 v 19 msec; p<0.01)
Transcutaneous oxygen saturationNo significant changes
Mean blood pressureLesser change in mean blood pressure in thiopental group (mean (SE) −2.9 [1.8] v 4.4 [1.1] mmHg; p<0.002)
Time taken to intubateSignificantly shorter in the thiopental group (mean (SE) 2.70 [0.37] v 5.08 [1.10] min; p<0.04)
Cook-Sather et al (1998), America476 infants semi-urgently or electively intubated. Three groups identified; one awake, one given a rapid sequence induction with thiopental (5–7 mg/kg) and muscle relaxant succinylcholine (2 mg/kg) and one group given a modified rapid sequence induction with thiopental and a muscle relaxant of either succinylcholine, vecuronium (0.1–0.2 mg/kg), rocuronium (0.6–1.0 mg/kg), or atracurium (0.4–0.5 mg/kg)Prospective, non-randomised, control trial (level 1b)Number of attempts at intubationSignificantly more attempts in awake group (8 for awake v 2 for rapid induction v 5 for modified induction where multiple attempts needed; p = 0.028)5 infants in the awake group had to be converted to the modified induction group
Time taken to complete intubationSignificantly longer in awake group (median 63 s for awake v 30 s for rapid induction v 36 s for modified induction; p = 0.004)
Heart rateNo significant difference
Oxygen saturationNo significant difference
ComplicationsNo significant difference
Millar and Bissonette (1994), Canada514 patients aged 1 to 42 days. Randomised into either awake intubation or thiopentone 5 mg/kg and succinylcholine 2 mg/kgRandomised control study (level 1b)Heart rateSignificantly elevated heart rate in awake group (+33 bpm; p<0.05)Lack of blinding. Small sample size. Patient age range up to 42 days in the article whereas up to 34 days in the abstract. Data from one patient was not included as it was incomplete. Randomisation method is not described
Systolic arterial blood pressureNo significant differences between the groups
Anterior fontanelle pressureSignificantly higher in awake group.(12 mmHg v 3 mmHg p<0.05)
Oxygen saturationNo significant differences
Cerebral blood flow velocityNo significant differences
Systolic peak flow velocityNo significant differences
Mean flow velocityNo significant differences
Diastolic peak flow velocityNo significant differences
Cerebrovascular resistanceNo significant differences
Pokela and Koivisto (1994), Finland620 newborn infants requiring elective tracheal intubation. Randomised to receive pethidine 1 mg/kg or alfentanil 20 μg/kg plus suxamethonium 1.5 mg/kg iv over 1 min. All neonates given glycopyrrolate 3–5 mg/kg 5 minutes before the procedureRandomised controlled trial (level 1b)HypoxaemiaHypoxaemia evident in all neonates in the pethidine group and 7 of 10 patients in the alfentanil groupLack of blinding. No method of randomisation documented. Small sample size. No quantification of ease of intubation
Duration of hypoxaemiaSignificantly longer in the pethidine group (4 min v 1.5 min; p = 0.036)
Time taken to intubateSignificantly longer in the pethidine group (120 seconds v 60 seconds; p = 0.012)
Success at first attempt3/10 intubations successful at first attempt in the pethidine group and 7/10 successful at first attempt in the alfentanil group
Change in mean arterial pressureNo significant difference
Change in heart rateNo significant difference
Change in plasma β-endorphin and serum cortisolNo significant difference
ApnoeaEvident in 3 patients in pethidine group
Ease of intubation and traumaEasier and less traumatic in alfentanil group
Khammash et al (1993), Canada728 infants randomised to receive atropine (0.02 mg/kg), atropine and succinylcholine (2 mg/kg), atropine and fentanyl (5 µg/kg), or atropine, succinylcholine, and fentanyl before non-urgent nasotracheal intubationRandomised control trial (level 1b)Intubation timeSignificantly reduced with succinylcholine and/or fentanyl versus atropine alone (22±7, 25±10, 27±7 v 50±22 seconds; p<0.05)Small sample size
Mean arterial pressureIncreased by ⩾20% after intubation in atropine and atropine/succinylcholine groups (p<0.05)
ComplicationsChest wall rigidity was found in 3 of the infants in the atropine and fentanyl alone group
Barrington et al (1989), Canada820 preterm neonates undergoing semi-elective intubation were randomised to awake and non-paralysed group or awake and paralysed with succinylcholine (2 mg/kg) group. Both received atropine (20 µg/kg)Randomised control trial (level 1b)Heart rateNo significant changesLack of blinding. Randomisation did not produce well matched groups with respect to the number of infants undergoing a tube change compared to the number undergoing initial intubation, so an additional 5 non-randomised infants undergoing awake intubation were included. Postnatal ages of succinylcholine group were significantly greater
Transcutaneous oxygen tensionSignificant fall in both groups during intubation. Higher for the awake and paralysed group than for the awake and non-paralysed group (86±46 torr v 55±23 torr p<0.05)
Blood pressureElevated in both groups. No significant difference during intubation between the groups
Intracranial pressureSignificantly greater rise in awake and non paralysed group than the awake and paralysed group (41.4±23.3 H2O v 36.8±11.6 cm H2O; p<0.05)
Cerebral perfusion pressureIncreased significantly in awake and paralysed group (mean 39.4 mmHg to 54.2 mmHg) versus the awake and non paralysed group
Charlton and Greenhough (1988), UK945 neonates needing semi-urgent or elective intubation for surgery. Patients were randomised into awake intubation group, N2O and halothane inhalation group, or thiopentone and muscle relaxant (atracurium or pancuronium) group.Randomised control study (level 1b)Blood pressure and heart rateNo significant changes in outcome between awake or anaesthetised groupsLack of blinding. Not randomised or matched for atropine administration. Small sample size. No preterm neonates. Randomisation not detailed.
Stow et al (1988), Canada1024 infants (less than 8 weeks post-natal age) electively intubated either awake or premedicated with sodium thiopentone 5 mg/kg and suxamethonium 2 mg/kg. Both groups were given atropine 0.02 mg/kg IVControl trial (level 1b)Anterior fontanelle pressure (AFP)Lesser increase in the premedicated than the awake groups (30 mmHg v 15 mmHg; p<0.05)Lack of blinding. Small sample size. Randomisation was not described. Groups not matched for post-conceptual age or weight
Heart rateNo significant changes
Systolic arterial pressureDecreased significantly in the premedicated infants during anaesthesia (from 92.5 mm Hg to 77.8 mmHg; p<0.05)
Friesen et al (1987), America1112 preterm neonates randomised into Group 1 (received atropine 0.02 mg/kg IV or Group 2 (received atropine 0.02 mg/kg IV, pancuronium 0.1 mg/kg IV, and 1 of 4 anaesthetics: 0.75% isoflurane, 0.5% halothane, 20 µg/kg fentanyl, or 2 mg/kg ketamineRandomised control trial (level 1b)Anterior fontanelle pressure (AFP)Increased significantly in group 1 (from 7.7 to 23.8 cm H2O; p<0.05), it did not change significantly in group 2. The changes in AFP were significantly different between group 1 and group 2 (+197% change v +25% change; p<0.05)Small sample size. Lack of blinding
Mean blood pressureSignificant increase in systolic blood pressure (average of 20%) in group 1 (p<0.05). Blood pressure did not change significantly in group 2
Kelly et al (1984), Canada1230 neonates requiring semi-urgent or elective intubation, 10 with either no drugs (control), atropine 0.01 mg/kg IV, or atropine 0.01 mg/kg IV and pancuronium 0.1 mg/kg IVRandomised control trial (level 1b)Heart rateDecrease was significantly greater for control and atropine groups than pancuronium group (52.2 bpm and 36.2 v 7.3; p<0.01)Lack of blinding. Small sample size
Transcutaneous oxygen saturationNo difference between the groups
Blood pressureNo reported difference between the groups
Intracranial pressureSignificant increase in all groups. Increase was significantly less in the atropine plus pancuronium group than in the other two groups (11.6 cm v 19.8 cm in control group v 24.8 cm in atropine group; p<0.05)
Raju et al (1980), America13Two groups of neonates and infants, one group (n = 4) intubated awake second group (n = 5) given halothane, nitrous oxide, and D-tubocurare muscle relaxant then intubatedControl study (level 1b)Intracranial pressureSignificant increase from the baseline in both groups after intubation (increase of 70.65±8.2 cm H2O; p<0.001 for awake and 19.45±5.1 cm H2O; p<0.05 for D-tubocurare). Significantly higher in infants intubated awake than those who received D-tubocurare (p<0.001)Small number of infants studied. Lack of blinding. Infants not matched for postnatal age or preoperative intracranial pressure. Randomisation method not described. Not all neonates (7 days to 10 months)
Barrington and Byrne (1998), Canada14269 consecutive nasotracheal intubations carried out on infants aged from 30 minutes–192 days. Premedication was given (atropine 20 µg/kg, fentanyl 3–4 µg/kg, and succinylcholine 2 mg/kg) if an IV was in place and if intubation was not an absolute emergencyCohort study (level 2b)Premedication usedOf the 269 intubations performed, premedication was used in 253 cases and not used in 16 casesNo control group. Large age range
Success rate253 premedicated intubations, 194 without incident, 28 required 2 attempts, and 9 required a second attempt with smaller tube
Incidence of complications and adverse events4 infants developed chest wall rigidity, resolved with succinylcholine in 3 cases, self limiting in the other
Naulaers (1997), Belgium1518 infants (gestational age 32–42 weeks postnatal age 1–150 days) weighing 1390–5000 g all received methohexital 2.6 mg/kg IVCohort study (level 2b)SedationAll patients adequately sedated within 2 minutes. 11/18 still sedated at 3 minutes and 4/18 at 5 minutes. All patients moving spontaneously by 10 minutesSmall sample size. No control group used. Infants not matched for gestational age, postnatal age, or weight. One patient received three doses of the drug, all others received one. Results were not assessed for significance
RelaxationAll patients adequately relaxed within 2 minutes. 12/18 still hypotonic at 3 minutes. 1 patient became hypertonic at 5 minutes, this lasted for 1 minute
Sleep12/18 patients were in a deep sleep after 3 minutes, 5/18 patients still asleep after 5 minutes. By 12 minutes all patients were awake