Key messages:
We did not find enough good-quality evidence about the best medicines to treat pain during endotracheal suctioning.
Overall, it is unclear if the medications studied in this review reduce negative effects (harms) such as blood pressure and heart rate changes, severe brain bleeding, or the length of time babies are on mechanical ventilators.
Larger, well-designed studies are needed to give better estimates of the benefits and potential harms of the different medications to treat pain during endotracheal suctioning.
What is endotracheal (lung) suctioning?
Many neonates (newborn babies) have difficulty breathing. To help them, a mechanical ventilator (breathing apparatus) is used. The ventilator works by inserting a flexible tube through the baby’s mouth or nose and down the windpipe (the trachea). The placement of the tube is known as an endotracheal procedure (meaning access is obtained via the trachea). While the baby is attached to the ventilator, the tube must be kept clean and clear. This process is called endotracheal suctioning.
What did we want to find out?
We wanted to find out how to reduce neonates' pain during endotracheal suctioning using pain-relieving or relaxing medications.
What did we do?
We searched medical databases for studies comparing two types of medicines to reduce neonates' pain during endotracheal suctioning. Medicines included opioid painkillers such as morphine and alfentanil; sedatives (relaxing medications) such as midazolam; and anaesthetics (medicines that slow down the brain and nervous systems' reactions to pain) such as ketamine.
What did we find?
We found seven studies of 1242 neonates. All studies took place in high-income countries. The largest study included 898 babies; the smallest included 10; one study included 150 babies, and the remaining four included fewer than 100 babies. No studies were supported financially by pharmaceutical companies.
Main results:
Outcomes during endotracheal suctioning
Opioids compared to placebo (a substance without medical effects)
It is unclear if morphine reduces pain or the length of time babies are on mechanical ventilation.
It is unclear if alfentanil reduces pain or heart rate.
Meperidine may reduce behavioural signs of pain such as crying.
Morphine may not cause low blood pressure.
Morphine probably reduces slightly the occurrence of severe brain bleeding.
Opioids compared to sedatives (midazolam)
It is unclear if morphine reduces pain.
Morphine may cause a large reduction in the length of time babies are on mechanical ventilation.
Morphine may not reduce the occurrence of severe cerebral haemorrhage (brain bleeding).
No studies reported blood pressure or heart rate changes, or behavioural signs of pain (such as crying).
Sedatives compared to placebo
Midazolam may reduce pain.
It is unclear if ketamine reduces pain, or affects heart rate or blood pressure.
It is unclear if midazolam reduces the length of time babies are on mechanical ventilation and decreases the occurrence of severe brain bleeding.
None of the studies reported on behavioural signs of pain.
What are the limitations of the evidence?
Confidence in our findings for our critical outcomes is low to very low because most studies were small, and there were too few studies to be certain about the results.
Opioids vs placebo:
We are not confident that opioids (morphine, alfentanil) reduce pain or change heart rate.
We have little confidence that opioids (meperidine) reduce behavioural signs of pain.
Opioids vs sedatives:
We are not confident that opioids (morphine) reduce pain.
Sedatives vs placebo:
We are not confident that ketamine reduces pain or affects heart rate; behavioural signs of pain were not measured.
We have little confidence that midazolam reduces pain.
How up to date is this evidence?
The evidence is up-to-date until August 2024.
Pročitajte cijeli sažetak
All newborns admitted to the neonatal intensive care unit (NICU) experience pain during routine care and are at increased risk of long-term adverse effects.
Endotracheal suctioning (ETS) is one of the most frequently performed procedures in the NICU, causing moderate-to-severe pain. Approximately 50% of extremely preterm neonates require intubation and repeated ETS.
Ciljevi
To evaluate the benefits and harms of pharmacological interventions for the prevention of pain during ETS in mechanically ventilated neonates.
Metode pretraživanja
We searched Cochrane CRS, MEDLINE, Embase, CINAHL and three trial registries, together with reference checking. The latest search date was August 2024.
Kriteriji odabira
We included randomised controlled trials (RCTs), quasi-, cluster- and cross-over RCTs of neonates (term and preterm) who were mechanically ventilated via endotracheal or tracheostomy tube and required ETS. Pharmacological interventions were compared to placebo, no intervention, or standard care, or to non-pharmacological interventions.
Prikupljanje podataka i obrada
Critical outcome measures were validated by composite pain scores. Secondary outcomes included physiological and behavioural pain indicators.
We used standard Cochrane methods. For continuous outcomes, we used a fixed-effect model and reported mean differences (MDs) with 95% confidence intervals (CIs). For categorical outcomes, we reported the typical risk ratio (RR) and risk difference (RD) and 95% CIs. We assessed the certainty of the evidence using GRADE.
Glavni rezultati
We included seven RCTs (1242 participants); six included preterm neonates; one included term neonates; four were included in a meta-analysis.
Opioids (morphine, alfentanil, meperidine) versus placebo (four studies)
The evidence is very uncertain for the following outcomes (all very low-certainty): morphine may have little to no effect on Premature Infant Pain Profile (PIPP) (MD -0.11; 95% CI -0.28 to 0.06; I2 = 93%; 4 studies, 1123 participants). The use of 20 µg/kg of alfentanil may reduce the pain score (CHEOPS) change from baseline (median = not specified (NS); IQR = NS; P = 0.031; 1 study; 10 participants). Results after 10 µg/kg of alfentanil were not reported. The use of 20 µg/kg of alfentanil may reduce heart rate change from baseline (median = NS; IQR = NS; P = 0.031; 1 study; 10 participants). Results after 10 µg/kg were not specified. Morphine may have little to no effect on the duration of mechanical ventilation (MD -4.70; 95% CI -11.07 to 1.67; I2 = not applicable (NA); 1 study, 45 participants).
Meperidine may reduce behavioural pain score (BPS) (MD -2.7; P = 0.001; 1 study, 84 participants; low-certainty). Morphine may not increase the risk of arterial hypotension (RR 1.49; 95% CI 95% 0.88 to 2.51; I2 = 57%; 2 studies, 928 participants; low-certainty).
Morphine probably does not reduce the incidence of severe intraventricular haemorrhage (IVH) (RR 1.13; 95% CI 0.80 to 1.61; I2 = 36%; I2 = 36%; 4 studies, 1065 participants; moderate-certainty).
No studies reported adverse events (AE) associated with morphine and meperidine; severe muscle rigidity was observed with alfentanil.
Opioids (morphine) versus sedatives (midazolam) (one study)
The evidence is very uncertain for the following outcomes (all very low-certainty): morphine may have little to no effect on PIPP score (MD -1.00; 95% CI -2.66 to 0.66; I2 = NA; 1 study, 46 participants); CHEOPS not reported. Morphine may result in a large reduction in the duration of mechanical ventilation (MD -6.70; 95% CI -12.40 to -1.00; I2 = NA; 1 study, 46 participants).
Morphine may not reduce the incidence of severe IVH (RR 0.08; 95% CI 0.00 to 1.43; 1 study, 46 participants; low-certainty).
No studies reported on physiological and behavioural indicators or haemodynamic changes.
No AEs were reported.
Sedatives (ketamine, midazolam) versus placebo (two studies)
Midazolam may reduce PIPP scores (MD -3.80; 95% CI -5.89 to -1.71; I2 = NA; 1 study, 45 participants; low-certainty).
The evidence is very uncertain for the following outcomes (all very low-certainty). Ketamine 0.5 mg/kg and 2 mg/kg may have little to no effect on CHEOPS change from baseline (P = NS; 1 study, 16 participants). Ketamine 1 mg/kg may reduce CHEOPS change from baseline (P = 0.043; 1 study, 16 participants). Ketamine 0.5 mg/kg and 1 mg/kg may have little to no effect on heart rate change from baseline (P = NS; 1 study, 16 participants). Ketamine 2 mg/kg may increase heart rate change from baseline (P = 0.029; 1 study, 16 infants). The use of 0.5 mg/kg, 1 mg/kg and 2 mg/kg ketamine may have little to no effect on mean arterial blood pressure change from baseline (P = NS; 1 study, 16 participants; very low-certainty). Midazolam may have little to no effect on the duration of mechanical ventilation (MD 2.00; 95% CI -5.14 to 9.14; I2 = NA; 1 study, 43 participants), and may have little to no effect on the risk of severe grade IVH (RR 1.59; 95% CI 0.43 to 5.84; I2 = NA; 1 study, 43 participants).
No studies reported behavioural indicators.
No AEs reported.
RoB assessment
Four studies had low RoB; three had high RoB: one for reporting bias; two for risk of carry-over effects.
Zaključak autora
Morphine may have little to no effect on PIPP or duration of ventilation (evidence very uncertain). Morphine may not increase the risk of hypotension and probably does not reduce the incidence of severe IVH. Alfentanil may reduce CHEOPS and heart rate change from baseline (evidence very uncertain). Meperidine may reduce BPS.
Compared to midazolam, morphine may have little to no effect on PIPP scores, and may result in a large reduction in the duration of ventilation (evidence very uncertain). No studies reported on physiological and behavioural indicators or haemodynamic changes. Morphine may not reduce the incidence of severe IVH, compared to midazolam (low-certainty evidence).
Compared to placebo, midazolam may reduce PIPP scores, and has little to no effect on the duration of ventilation or on the risk of severe IVH (low to very low-certainty evidence); ketamine may reduce CHEOPS change, and have little to no effect on heart rate change, or on mean arterial blood pressure (evidence very uncertain). No studies reported on behavioural indicators or haemodynamic outcomes.
