Premedication for semi-urgent intubation
| Citation, country | Study group | Study type (level of evidence) | Outcome | Key results | Study weaknesses |
|---|---|---|---|---|---|
| Lemyre et al (2004), Canada1 | 34 infants randomly assigned to receive morphine 0.2 mg/kg IV or placebo (0.9% sodium chloride), for elective intubation | Double blind randomised control trial. (level 1b) | Duration of severe hypoxaemia | No significant difference | Different levels of experience of people performing the intubations (help called). Variations in time of preoxygenation and hand ventilation |
| Duration of hypoxaemia | No significant difference | ||||
| Duration of procedure | No significant difference | ||||
| Max increase in mean blood pressure | No significant difference | ||||
| Number of attempts | No significant difference | ||||
| Number where intubation was achieved at first attempt | No significant difference | ||||
| Number where intubation needed a rescue intubator | No significant difference | ||||
| Bradycardia during procedure | No significant difference | ||||
| Oei et al (2002), Australia2 | 20 infants randomised to awake intubation or premedication with morphine 100 μg/kg, atropine 10 μg/kg and suxamethonium 1 mg/kg | Non-blinded randomised control trial (level 1b) | Heart rate | Significantly 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 saturation | No significant difference | ||||
| Total time taken to complete intubation | Significantly shorter in premedicated infants (median 60.5 seconds v 595 seconds; p = 0.016) | ||||
| Number of attempts at intubation | More than twice as many attempts in the awake group (p = 0.01) | ||||
| Bhutada et al (2000), America3 | 30 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 saline | Randomised, placebo controlled trial (level 1b) | Heart rate | Significant changes (mean (SE) −0.5 [4.4] v 12.0 [3.2] bpm; p<0.03) | Lack of blinding. Small sample size |
| Heart rate variability | Significantly less variable in study group (mean (SE) −2.0 v 19 msec; p<0.01) | ||||
| Transcutaneous oxygen saturation | No significant changes | ||||
| Mean blood pressure | Lesser 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 intubate | Significantly 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), America4 | 76 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 intubation | Significantly 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 intubation | Significantly 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 rate | No significant difference | ||||
| Oxygen saturation | No significant difference | ||||
| Complications | No significant difference | ||||
| Millar and Bissonette (1994), Canada5 | 14 patients aged 1 to 42 days. Randomised into either awake intubation or thiopentone 5 mg/kg and succinylcholine 2 mg/kg | Randomised control study (level 1b) | Heart rate | Significantly 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 pressure | No significant differences between the groups | ||||
| Anterior fontanelle pressure | Significantly higher in awake group.(12 mmHg v 3 mmHg p<0.05) | ||||
| Oxygen saturation | No significant differences | ||||
| Cerebral blood flow velocity | No significant differences | ||||
| Systolic peak flow velocity | No significant differences | ||||
| Mean flow velocity | No significant differences | ||||
| Diastolic peak flow velocity | No significant differences | ||||
| Cerebrovascular resistance | No significant differences | ||||
| Pokela and Koivisto (1994), Finland6 | 20 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 procedure | Randomised controlled trial (level 1b) | Hypoxaemia | Hypoxaemia evident in all neonates in the pethidine group and 7 of 10 patients in the alfentanil group | Lack of blinding. No method of randomisation documented. Small sample size. No quantification of ease of intubation |
| Duration of hypoxaemia | Significantly longer in the pethidine group (4 min v 1.5 min; p = 0.036) | ||||
| Time taken to intubate | Significantly longer in the pethidine group (120 seconds v 60 seconds; p = 0.012) | ||||
| Success at first attempt | 3/10 intubations successful at first attempt in the pethidine group and 7/10 successful at first attempt in the alfentanil group | ||||
| Change in mean arterial pressure | No significant difference | ||||
| Change in heart rate | No significant difference | ||||
| Change in plasma β-endorphin and serum cortisol | No significant difference | ||||
| Apnoea | Evident in 3 patients in pethidine group | ||||
| Ease of intubation and trauma | Easier and less traumatic in alfentanil group | ||||
| Khammash et al (1993), Canada7 | 28 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 intubation | Randomised control trial (level 1b) | Intubation time | Significantly 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 pressure | Increased by ⩾20% after intubation in atropine and atropine/succinylcholine groups (p<0.05) | ||||
| Complications | Chest wall rigidity was found in 3 of the infants in the atropine and fentanyl alone group | ||||
| Barrington et al (1989), Canada8 | 20 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 rate | No significant changes | Lack 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 tension | Significant 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 pressure | Elevated in both groups. No significant difference during intubation between the groups | ||||
| Intracranial pressure | Significantly 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 pressure | Increased 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), UK9 | 45 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 rate | No significant changes in outcome between awake or anaesthetised groups | Lack of blinding. Not randomised or matched for atropine administration. Small sample size. No preterm neonates. Randomisation not detailed. |
| Stow et al (1988), Canada10 | 24 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 IV | Control 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 rate | No significant changes | ||||
| Systolic arterial pressure | Decreased significantly in the premedicated infants during anaesthesia (from 92.5 mm Hg to 77.8 mmHg; p<0.05) | ||||
| Friesen et al (1987), America11 | 12 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 ketamine | Randomised 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 pressure | Significant 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), Canada12 | 30 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 IV | Randomised control trial (level 1b) | Heart rate | Decrease 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 saturation | No difference between the groups | ||||
| Blood pressure | No reported difference between the groups | ||||
| Intracranial pressure | Significant 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), America13 | Two 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 intubated | Control study (level 1b) | Intracranial pressure | Significant 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), Canada14 | 269 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 emergency | Cohort study (level 2b) | Premedication used | Of the 269 intubations performed, premedication was used in 253 cases and not used in 16 cases | No control group. Large age range |
| Success rate | 253 premedicated intubations, 194 without incident, 28 required 2 attempts, and 9 required a second attempt with smaller tube | ||||
| Incidence of complications and adverse events | 4 infants developed chest wall rigidity, resolved with succinylcholine in 3 cases, self limiting in the other | ||||
| Naulaers (1997), Belgium15 | 18 infants (gestational age 32–42 weeks postnatal age 1–150 days) weighing 1390–5000 g all received methohexital 2.6 mg/kg IV | Cohort study (level 2b) | Sedation | All 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 minutes | Small 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 |
| Relaxation | All 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 | ||||
| Sleep | 12/18 patients were in a deep sleep after 3 minutes, 5/18 patients still asleep after 5 minutes. By 12 minutes all patients were awake |