Table 3. Summary of procedures and recommendedations for pain relief.

Skin-breaking Procedures	Proposed interventions	Comments
Heelstick	Use non-pharmacologic measures + mechanical lance, squeezing the heel is the most painful phase	Venipuncture is more efficient, less painful; Local anesthetics, acetaminophen, heel warming do not reduce heelstick pain
Venipuncture	Non-pharmacologic measures, use topical local anesthetics	Requires less time & less resampling than heelstick
Arterial puncture	Non-pharmacologic measures, use topical and sub-cutaneous local anesthetics	More painful than venipuncture
Intravenous cannulation	Non-pharmacologic measures, use topical local anesthetics
Central line placement	Non-pharmacologic measures, use topical local anesthetics, consider low-dose opioids or deep sedation based on clinical factors	Some centers prefer using general anesthesia
Finger stick	Non-pharmacologic measures and use mechanical device	Venipuncture is more efficient, less painful; Local anesthetics, acetaminophen, or warming may not reduce finger stick pain
Subcutaneous injection	Avoid if possible, use non-pharmacologic measures and topical local anesthetics if procedure cannot be avoided
Intramuscular injection	Avoid if possible, use non-pharmacologic measures and topical local anesthetics if procedure cannot be avoided
Lumbar puncture	Non-pharmacologic measures and topical local anesthetic, Lidocaine infiltration, careful positioning	Use IV analgesia/sedation, if patient is intubated and ventilated
Peripheral arterial line	Non-pharmacologic measures and topical local anesthetic, Lidocaine infiltration, consider IV opioids
Circumcision	Non-pharmacologic measures and topical local anesthetic, Lidocaine infiltration, IV/PO acetaminophen pre- and post-procedure	Lidocaine infiltration for distal, ring, or dorsal penile nerve blocks (DPNB); liposomal lidocaine is more effective than DPNB
Suprapubic bladder aspiration	Non-pharmacologic measures and topical local anesthetic, Lidocaine infiltration, consider IV fentanyl (0.5-1 mcg/kg)
Arterial or venous cutdown	Non-pharmacologic measures and topical local anesthetic, Lidocaine infiltration, IV fentanyl (1-2 mcg/kg), consider deep sedation	Most arterial or venous cutdowns can be avoided, consider referral to Interventional Radiology
Peripherally inserted central catheter (PICC)	Non-pharmacologic measures and topical local anesthetic, Lidocaine infiltration, consider IV fentanyl (1 mcg/kg) or IV ketamine (1 mg/kg)	Some centers prefer using deep sedation or general anesthesia
ECMO Cannulation	Propofol 2-4 mg/kg, Ketamine 1-2 mg/kg, fentanyl 1-3 mcg/kg, muscle relaxant as needed
Skin-breaking Procedures	Proposed interventions	Comments
Tracheal intubation (e.g., for mechanical ventilation)	Give fentanyl (1 mcg/kg) or morphine (10-30 mcg/kg), with midazolam (50-100 mcg/kg), ketamine (1 mg/kg), use muscle relaxant only if experienced clinician, consider atropine	Superiority of one drug regimen over another has not been investigated
Gastric tube insertion	Non-pharmacologic measures, consider local anesthetic gel	Perform rapidly, use lubricant, avoid injury
Chest physiotherapy	Gentle positioning, Fentanyl (1 mcg/kg) if a chest tube is present	Avoid areas of injured or inflamed skin, areas with indwelling drains or catheters
Removal of intravenous catheter	Solvent swab, consider non-pharmacologic measures
Wound treatment	Non-pharmacologic measures, use topical local anesthetics, consider low-dose opioids, or deep sedation based on extent of injury	See also “dressing change”
Umbilical catheterization	Non-pharmacologic measures, IV acetaminophen (10 mg/kg), avoid sutures to the skin	Cord tissue is not innervated, but avoid injury to skin
Bladder compression	Consider non-pharmacologic measures or IV acetaminophen (10 mg/kg) if severe or prolonged
Tracheal extubation	Use solvent swab for tape, consider non-pharmacologic measures
Dressing change	Non-pharmacologic measures and topical local anesthetic, consider deep sedation if extensive

^*Nonpharmacologic measures include: pacifier, oral sucrose, swaddling, skin-to-skin contact with mother

^*The frequency of procedures can be reduced without sacrificing the quality of neonatal intensive care.