Clonidine for painful procedures and conditions in infants

Review question: does clonidine administration reduce pain in newborns exposed to painful procedures or conditions?

Background: newborns admitted to the hospital are exposed to a number of painful procedures which might include blood sampling, lumbar puncture (a medical procedure where a needle is inserted into the spinal canal, usually to collect cerebrospinal fluid for testing), tubes in the stomach, different types of catheters, and minor surgical procedures such as neonatal circumcision. In addition, newborns might have pain because of clinical conditions, such as, fractured bone, pain following traumatic vaginal birth, disease of the skin (open skin lesions from an inherited skin disorder), or intestines (necrotising enterocolitis (inflammation)). All babies, and especially those born too early (preterm), are very sensitive to pain. Moreover, the experience of repeated episodes of pain might cause problems, such as an altered development of the nervous system, in early life and an increased pain sensitivity when they grow up. Most of the medicines to manage pain and stress in babies have side effects, and might also harm the immature developing brain by inducing death of cells (apoptosis) in the brain.

Study characteristics: we searched for studies up to 11 March 2020. The aim of this review was to assess if clonidine could reduce pain in newborns. This medicine can be given through injections, using a tube in the stomach (nasogastric tube), through the skin, and as spinal anaesthesia. However, the latter is not in the focus of this review as it is used for babies undergoing specific surgical procedures. Clonidine works on the brain modifying responses and reducing stress and agitation. Furthermore, clonidine may reduce pain, especially if used in combination with other medicines.

Key results: we found no studies for our review. Three studies were excluded because clonidine was given for spinal anaesthesia, whereas our review focuses on other indications.

Authors' conclusions: 

We did not find any studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of clonidine for the prevention or treatment of procedural or postoperative pain, or pain associated with clinical conditions in neonates.

Read the full abstract...

Critically ill newborn infants undergo a variety of painful procedures or experience a variety of painful conditions during their early life in the neonatal unit. In the critically ill paediatric and neonatal population, clonidine is prescribed as an adjunct to opioids or benzodiazepines aiming to reduce the doses of these drugs that are required for analgesia or sedation, or to facilitate weaning from mechanical ventilation. It has been shown that clonidine premedication might have a positive effect on postoperative pain in children.


To assess the benefit and harms of clonidine for the prevention or treatment of procedural pain; postoperative pain; or pain associated with clinical conditions in non-ventilated neonates.

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the CENTRAL, MEDLINE via PubMed, Embase, and CINAHL to December 2018. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We ran an updated search from 1 January 2018 to 11 March 2020 in CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost.

Selection criteria: 

Randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing clonidine to placebo or no treatment, opioids, paracetamol, dexmedetomidine, or non-pharmacological pain-reducing interventions for the management of procedural pain, postoperative pain, and pain associated with clinical conditions in preterm and term newborns.

Data collection and analysis: 

Two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, modality of administration, and dose of clonidine) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcome considered was pain: for procedural pain, the mean values of each analgesia scale assessed during the procedure and at one to two hours after the procedure; for postoperative pain and for pain associated with clinical conditions, the mean values of each analgesia scale assessed at 30 minutes, three hours, and 12 hours after the administration of the intervention. We planned to use the GRADE approach to assess the quality of evidence.

Main results: 

Our search strategy yielded 3383 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. We excluded three trials where clonidine was administered for spinal anaesthesia.