<p>That newborns and infants perceive pain is no longer a matter of debate. There is mounting evidence suggesting negative consequences of untreated and recurrent pain in newborns. There have been several recent consensus statements concerning neonatal pain (<xref ref-type="bibr" rid="bib001">1</xref>–<xref ref-type="bibr" rid="bib005">5</xref>). This paper draws extensively from these references, in particular the most recent two, evidence-based statements (<xref ref-type="bibr" rid="bib001">1</xref>,<xref ref-type="bibr" rid="bib002">2</xref>).</p><sec id="sec002"><title>Developmental neurobiology and pharmacology

Journal of Neonatology

0971-2179

National Neonatology Forum

jn-20-4-010

Neonatal Surgery

Neonatal pain in Surgical Neonate

Agarwal

Aparna

Dept. of Anaesthesia, Sir Ganga Ram Hospital, New Delhi. E-mail: apsin@hotmail.com

10–122006

204363376

<p>That newborns and infants perceive pain is no longer a matter of debate. There is mounting evidence suggesting negative consequences of untreated and recurrent pain in newborns. There have been several recent consensus statements concerning neonatal pain (<xref ref-type="bibr" rid="bib001">1</xref>–<xref ref-type="bibr" rid="bib005">5</xref>). This paper draws extensively from these references, in particular the most recent two, evidence-based statements (<xref ref-type="bibr" rid="bib001">1</xref>,<xref ref-type="bibr" rid="bib002">2</xref>).</p><sec id="sec002"><title>Developmental neurobiology and pharmacology

Fitzgerald and Pattinson in separate studies have demonstrated that neonates clearly perceive pain (6–8). They showed integrated behavioral and physiologic responses to nociceptive stimuli. They further demonstrated that neonates might have exaggerated response to pain as descending inhibitory pathways to the dorsal horn of spinal cord are underdeveloped at birth. Moreover, the receptive areas are wider and excitatory thresholds are lower in them. Fitzgerald in a separate work further demonstrated that recurrent painful stimuli such as heel lancing, intravenous line placement etc further lower the thresholds of the dorsal horn neurons (8). In the past, lack of myelination was proposed as an index of immaturity of the neonatal central nervous system and was used to support the argument that premature and full term neonates are not capable of perceiving pain (9–18). Major nociceptive neurons in the newborns as well as adults are either unmyelinated C fibers or thinly myelinated A-α fibres (19). Even though pain transmission is slower in this population the nociceptive input to brain does occur.

Untreated pain in neonates has been shown to cause exaggerated physiologic and behavioral responses to noxious events (7,18,19). The developmental pharmacology of neonates is very different from that of older children and adults. Higher body water content in them results in larger volume of distribution of all water soluble drugs, and hence longer duration of their action. Less muscle and fat leads to less tissue uptake and higher plasma concentration. This is further complicated by lower levels of plasma albumin and α-1 acid glycoprotein which means higher blood levels of opioids and local anesthetics, hence more propensity to drug toxicity (20,21). Also higher cerebral blood flow and immaturity of the blood brain barrier facilitates drug delivery to the brain. At birth, the hepatic enzyme system responsible (22) for phase 1 reactions i.e. cytochrome P-450 which is responsible for metabolism of many NSAIDS and opioids, is under developed (23). Renal functions of neonates particularly premature neonates are also subnormal; hence the parent compounds as well as their metabolites tend to accumulate to toxic levels (19,20).

Physiological and behavioral response of a neonate to ongoing pain

Neonates lack the ability to report pain and this contributes to the failure to recognize and treat pain on the part of health care professionals (2326). As they cannot verbalize pain they depend on others to recognize, assess and manage their pain (27). Most NICUs still subject neonates to painful procedures without providing adequate analgesia. Pain is not just simple transmission of neural impulses from the periphery to the cerebral cortex (21). Signals to the cortex can be attenuated and augmented at different levels. Nociceptive pathways have synapses in the limbic system, frontal cortex, and medial thalamus where they can be influenced by emotions, behavior, past experiences, cultural orientation and emotional state. A successful acute pain management targets all the elements in the complex system of pain transduction, transmission, modulation and perception. Most attention has been given to acute noxious stimuli due to procedures such as circumcision, heel lancing and awake intubation. Even these short stimulus, has been shown to cause large fluctuations in pO₂, increases in heart rate, arterial blood pressure and intracranial tension (28).

Surgery without sufficient analgesia results in the release of stress hormones, including catecholamines, corticosteroids, growth hormones and glucagon, which stimulate a cascade of metabolic changes. These result in a breakdown of proteins, fat and carbohydrates, producing a catabolic state and negatively influencing the repair of injured tissues. Anand et al. showed that preoperative suppression of stress response by strong analgesics results in decreased incidence of sepsis and metabolic acidosis, and post operative deaths (29).

Studies by Taddio (30,31) have indicated that pain experienced early in life by term infants may exaggerate affective and behavioral responses during subsequent painful events. Johnston showed that neonates who were exposed to multiple painful and noxious stimuli between postconcepional weeks 28–32 showed different behavioral and physiological responses to pain as compared to neonates of similar age who had not had such exposures (32). There is clinical data to support long-term effects of untreated neonatal pain and stress. Painful stimuli experienced during neonatal period are recorded biologically and have been shown to alter brain development and subsequent behavior (18,19,32–34). Table 1 lists all the responses to ongoing pain. Table 1

Responses of Neonates to Pain.

Physiological Changes:	Behavioral changes:	Hormonal changes:	Autonomic changes	Body movements

Heart rate ↑	Grimacing	Cortisol	Mydriasis	Finger clenching
Blood pressure↑	Screwing up of eyes	Catecholamines
Respiratory rate↑	Nasal flaring	Glucagon	Sweating	Thrashing Writing
Oxygen consumption↑	Deep nasolabial groove	Growth hormone
Mean airway pressure↑	Curving of the tongue	Renin	Flushing	Arching of back
Muscle tone↑	Quivering of the chin	Aldosterone
Intracranial pressure↑		Antidiuretic hormone	Pallor	Head hanging
		Decreased secretion of Insulin

Pain Assessment Tools

A major aspect in which neonates are different from older patients is that they are non-verbal. In case of neonates, pain assessment is the responsibility of the caregiver. An effective pain assessment tool should enable the caregiver to assess and objectively quantify pain and also assess the effectiveness of any intervention. Several validated and reliable pain measures exist to assess acute pain in term and preterm neonates (35).

The behavioral indicators of pain (facial expression, body movements and crying) and physiological indicators (changes in heart rate, respiratory rate, blood pressure, oxygen saturation, vagal tone, and palmar sweating and plasma cortisol or catecholamine levels) have been used to assess and manage pain and stress in neonates. Several composite measures have been described vide infra. These have been summarized in Table 2. Table 2

Pain Assessment Tools (2)

	Premature Infant Pain Profile (PIPP)	Neonatal Facial Coding System (NFCS)	Neonatal Infant Pain Scale (NIPS)	CRIES Score

Variables assessed	Gestational age	Brow bulge	Facial expression	Crying Requires increased oxygen administration
	Behavioral state	Eye squeeze	Cry Breathing patterns
	Heart Rate	Nasolabial furrow
	Oxygen saturation	Open lips	Arms Legs	Increased vital
	Brow bulge	Stretch mouth	State of arousal	signs Expressions
	Eye squeeze	Lip purse		Sleeplessness
		Taut tongue
		Tongue protrusion
Reliability data	Interrater and intrarater reliability >0.93	Interrater and intrarater reliability >0.85	Interrater reliability >0.92	Interrater reliability >0.72
Forms validity established	Face, content, construct, (in preterm and term neonates)	Face, content, construct, and convergent (r=0.89)	Face, content, construct, and concurrent (r=0.53–0.84)	Face, content, discrimination and concurrent (r=0.49–73)
Clinical utility	Feasibility and utility established at bedside	Feasibility established at bedside	Not established*	Nurses prefer CRIES over other scales.

Premature Infant Pain Profile (PIPP): Includes facial actions such as brow bulge, eyes squeezed shut, nasolabial furrow, and physiological indicators including heart rate, oxygen saturation in context of gestational age and neonatal state (36).

CRIES: This assesses Crying, Requirement for oxygen supplementation (i.e., when SpO2<95%), Increase in heart rate and blood pressure, facial Expression and Sleeplessness (37).

Neonatal Infant Pain Scale (NIPS): This assesses facial expression, cry, breathing patterns, movements of arms and legs, and state of arousal (38).

There are several unidirectional measures also which use multiple indicators such as Neonatal Facial Coding System: (NFCS) (39). Grunau, in his work on bedside application of neonatal facial coding system showed that facial display is more specific to tissue damage compared to heart rate also it has higher inter-observer reliability. Hudson (40) conducted a study to establish the validityand clinical usefulness of Pain Assessment In Neonates (PAIN) as compared to NIPS and suggested that PAIN is a valid tool.

In a very recent study Suraseranivongse et al. (41) compared postoperative pain scales (CRIES, CHIPPS and NIPS) in neonates. The comparison was in terms of validity, reliability and practicality. They concluded that all scales yield good agreement with routine decisions to treat postoperative pain. However, in terms of practicality NIPS was found to be the most acceptable valid and reliable tool.

There is paucity of measures to evaluate pain in very low birth weight neonates or those who require mechanical ventilation (42,43). However, Grunau in his work on low birth weight babies found that some extensor movements seemed to be distress signals, whereas tremors, startles, and twitches are not signals to tissue invasive events (44).

Each of the pain assessment instruments discussed above has strengths and limitations. For optimally using a tool the health care professionals should be familiarized with its use and this should be systematically integrated into the institutions’ policies. This would maintain reliability of the tool, and allow timely intervention thereby minimizing unnecessary suffering in the postoperative neonate.

Approach to Pain Management in a Surgical Neonate

Advances in medical technology have led to an increase in number of premature and full term babies presenting for major surgeries. Due to the underlying illness surgical neonates are likely to undergo repetitive painful procedures and may lack the traditional responses to pain, such as crying and grimacing. This problem is further compounded in premature and low birth weight newborns that are more vulnerable to the effects of pain. Concerns over treatment modalities, adverse reactions, potential long term detrimental effects and limited long term follow up often limit the adequate treatment of pain in this population. Improved attention has been made with efforts to minimize noxious stimuli such as noise, light and excessive handling. Infants still undergo painful procedures without adequate analgesia.

General Anaesthesia

To a large extent, management of surgical stress response in neonates can be accomplished by pharmacologic interventions that characterize anesthetic care of surgical patients. General anesthesia for preterm and term neonates has been rendered safe due to advancements in anaesthetic medications, techniques and monitoring. It aims at providing analgesia, amnesia and muscle relaxation during surgery. Analgesia can be extended into the postoperative period. Anand demonstrated that blood levels of hormonal and metabolic indicators of stress response were significantly lower in neonates receiving general anesthetics during surgery.

Nitrous oxide analgesia

Nitrous oxide is an anesthetic gas with significant analgesic and some amnesic and anxiolytic properties. It has a rapid and predictable onset and offset of action and can safely be titrated to produce a state of “conscious sedation”. It is now commonly being used for procedural sedation in emergency units. This can be administered via demand valve or via a continuous flow device. Continuous flow devices require the continuous presence of a qualified person to monitor for signs of over sedation. For administering nitrous oxide availability of complete resuscitation equipment and qualified anaesthesia personnel is advised.

Midazolam

Newborn babies undergoing uncomfortable procedures in intensive care units may need sedation to reduce stress and avoid complications. Midazolam is a short acting sedative increasingly used in neonatal intensive care. A review of trials found no evidence to support the use of midazolam as a sedative for neonates undergoing intensive care. Babies receiving midazolam stayed in hospital longer and had more adverse effects. More research is needed urgently into the safety and effect of midazolam in neonates (45,46).

Opioids

Narcotics are not complete anaesthetics and don't provide muscle relaxation or amnesia, which are essential aspects of complete anaesthetic. Narcotic based anesthetic techniques are commonly used during cardiovascular procedures in neonates. They remain the most common means of achieving pain control in the surgical neonate. With a well constructed pain management plan their usage however will not affect the postoperative outcome. The risk of apnea cannot be ignored as the neonates are particularly vulnerable to respiratory depressant effects of opioids. Fast passage via open ductus venosus and the immaturity of the liver, results in longer elimination half life. The blood brain barrier is more permeable to hydrophilic drugs like morphine. Dosage regimens of commonly used opioids in neonates have been listed in Table 3. Table 3

Opioid Dosing Regimens

Drug	Route	Dose/Interval

Morphine	Oral, immediate release	0.3 mg/kg every 3–4 h
	Oral, sustained release	0.25–0.5 mg/kg every 8–12 h
	IV bolus:
	Preterm neonate	10–25 μg/kg every 2–4 h
	Full-term neonate	25–50 μg/kg every 3–4 h
	IV Infusion:	2–5 μg/kg/h
	Preterm neonate	5–10 μg/kg/h
	Full-term neonate	10–15 μg/kg (oralet)
Fentanyl	Oral/transmucosal/Intranasal	1–2 μg/kg
	IV bolus	0.5–1 μg/kg/1–2 hr
	IV infusion	0.5 μg/kg/hr

Opioids are used for moderate to severe nociceptive pain, although they are sometimes used for neuropathic pain. Common effects are respiratory depression, sedation, nausea, vomiting, pruritus, urinary retention, ileus, and constipation, seizures, muscle rigidity and myoclonic movements (22,47). Morphine is most commonly used for craniotomy, thoracotomy, sternotomy and laparotomy. There is significant individual variability in the side-effect profiles of the different opioid analgesics. In the presence of unacceptable side effects, switching to a different opioid may result in lessened side effects (48). Therefore, careful titration of morphine is required to obtain the desired level of analgesia while monitoring side effects (49–53). Commonly used opioids include morphine, fentanyl, sufentanil and remifentanil.

Non-opioid Analgesics

Ketamine: It is a phencyclidine derivative which produces amnesia and intense analgesia. Beneficial effects include bronchodilatation and less depression of respiration. Adverse effects include increased salivary and tracheobronchial secretions, cerebral vasodilatation, and apnea in neonates with raised intracranial tension (54,55). There are conflicting reports on the use of ketamine in neonates.

A combination of opioids, regional techniques and acetaminophen is being successfully used in neonates. This balanced approach results in reduction in systemic opioid administration thus minimizing their side effects. During rest the analgesic requirements are much less than when attempting to change positions, coughing, dressing changes, therapeutic and diagnostic tests, physiotherapy and nursing. Effective pain management should include a proactive plan for managing background and breakthrough pain (56). Non-opioid pain management modalities are important in pain management of the postoperative neonate.

Acetaminophen is useful either as a sole analgesic for mild discomfort or as an adjuvant for moderate to severe pain when narcotic or regional analgesia is employed. It lacks the troublesome side effects of NSAIDS. Careful attention to dosing is essential (Table 4). Table 4

Acetaminophen Dosages

Preparation	Dose	Interval dosage	Maximum daily

Drops (80 mg/0.1 ml) Suppositories (80 mg, 120 mg)	Oral: 10–15 mg/kg Rectal single dose: 35–45 mg/kg repeated dose: 20 mg/kg	Every 4 hrs Full term: every 6 hrs Preterm: every 12 hrs	Newborns >32 wks PCA:60mg/kg/28–32 wks 40mg/kg/day

When used in combination with opioids it reduces their requirement and hence hastens postoperative recovery. Rectal route is a useful option; this is associated with lower plasma levels and longer elimination half life. A dose of 20–35 mg/kg is recommended for the initial preincision and immediate postoperative phase.

In general, the risk-benefit profile with the use of non-steroidal anti-inflammatory drugs (NSAIDS) does not favour their use in neonates. Potential complications include renal toxicity, necrotizing enterocolitis, platelet dysfunction, and hemorrhage esp. intracranial (57).

Regional Pain Control Techniques

These are increasingly being employed to reduce requirement of intraoperative opioids and manage postoperative pain in neonates. Regional anesthetic techniques are an alternative that continue to increase in popularity. Depending on the site of surgery and the severity of the postoperative pain, this may include a neuraxial approach (caudal, lumbar, or thoracic epidural) or a peripheral nerve block. For unilateral surgery, a peripheral nerve block may be chosen. For outpatients, a single shot approach using only local anesthetic agents is used, such as a caudal epidural block with bupivacaine following inguinal herniotomy. For the inpatient, more prolonged analgesia can be provided by a single shot approach using a combination of local anesthetic with opioid (morphine) or clonidine or by the placement of a catheter for a continuous infusion. Whenever neuraxial opioids are administered, ongoing monitoring of respiratory status is suggested given the potential for respiratory depression.

Local Infiltration Anesthesia

Some procedures in superficial areas can be accomplished with infiltration of local anesthetic in the area. Pain relief continues into the postoperative phase and reduces the need for systemic medication. Surgical wound infiltration can be used to provide analgesia for virtually all procedures where other regional blocks are either inappropriate or contraindicated.

While administering local anaesthetic in any form safe dosage limit should be maintained (Table 5). Table 5

Maximum Doses of Local Anesthetic Agents

Local anesthetic	Spinal (mg/kg)	Epidural (mg/kg)	Reripheral (mg/kg)

Tetracaine	1	NR	NR
Lidocaine	NR	5–7^a	5–7^a
Bupivacaine	0.5	2.5	2.5
Ropivacaine	NR	2.5–3	2.5–3
2-Chloro procaine	NR	20–30	NR

NR: Not Recommended
a: higher doses only with adrenaline 1:2, 00,000

Topical anaesthesia

Direct application of a local anesthetic agent to the site of action, commonly the skin, conjunctiva, mucous membranes and open wounds.

Eutectic Mixture of Local Anaesthetics (EMLA): It is a cream with a combination of lignocaine and prilocaine. Maximum safe dose in neonates is <1 gm i.e. an area of 10 cm². The use of EMLA cream is usually safe in neonates and infants who do not have coexisting diseases that may predispose to methemoglobinemia, such as Hemoglobinopathies, Glucose-6-phosphate dehydrogenase deficiency and exposure to aniline dyes and oxidants.

Non-pharmacologic interventions

These are considered central to the pain management of neonates. Modalities such as bundling, holding, and rocking the neonate, provision of a pacifier to alleviate distress, and minimization of environmental stimuli such as extraneous noise and unnecessary light. Sucrose has been documented to reduce pain and distress in term as well as preterm newborns. Administration of 15–50% sucrose is effective in neonates and may be effective up to 2 months of age. Systematic reviews of the literature suggests doses of 0.5–1.0ml of 24% sucrose in 0.25ml aliquots, commencing 2 minutes before the procedure. Concomitant use of a pacifier may further reduce behavioral responses to painful stimuli. A pacifier should only be used in accordance with parental wishes and its one-off use is not intended to promote or encourage regular pacifier use in infants (58–60,73,95–98).

Painful Procedures in a Surgical Neonate

Despite advances in pain management, prevention and treatment of unnecessary pain attributable to anticipated noxious stimuli remain limited (61–63). A multimodal approach has been shown to have a synergistic effect (64). Multisensory stimulation may include massage, eye contact, use of a soothing/familiar voice or familiar smell. This multimodal approach as per recommendations of AAP 2000 (American Academy of Pediatrics for prevention of pain and stress in neonates) has been summarized in Table 6. Table 6

Ongoing Analgesia for Neonatal Procedural Pain

Reduce acoustic, thermal, and other environmental stresses

Use swaddling or containment, by holding the infant ± multisensory stimulation

Use a pacifier and if possible and safe to do so give with sucrose (do not use routine, repeated doses of sucrose in infants < 31 weeks gestation)

Consider low-dose continuous infusion of morphine if patient is ventilated although this may not be indicated in preterm infants (the use of midazolam is not recommended)

Commonly performed procedures in a surgical neonate

Tables 7 and 8 list the commonly performed painful procedures and general principles of pain management in a surgical neonate respectively. (Adapted from Anand 2001 (2) and Bell 1994 (5) and supported by evidence listed in AAP 2000 (3). Blood sampling is commonly achieved with venepuncture or heel lancing. Venepuncture is the preferred method and has been shown to be less painful and requires less resampling. EMLA cream (0.5–1.0g) should be applied, 60–90 minutes prior. Oral sucrose (12–24%) with concomitant pacifiers needs to be encouraged. This should commence 2 minutes prior to the procedure, or mother should be encouraged to breast/bottle feed during the procedure. Parent/care giver should hold and employ multisensory stimulation. Swaddling, containment by flexing and holding the infant should be encouraged and multisensory stimulation should be employed. Heel lancing: Heel should not be warmed as it does not reduce pain or aid blood collection. Use of oral sucrose, breast/bottle feed needs to be encouraged. Parent/care giver should hold and employ multisensory stimulation. Automated lancet, preferably fully retractile should be used. EMLA is ineffective for heel lancing as heel squeezing is the most painful part of the procedure (64,72–75,94,95). Table 7

Painful Procedures in a Surgical Neonate

Diagnostic	Therapeutic	Surgical

Arterial puncture	Bladder catheterization	Other surgical procedures e.g. peritoneal drain, cut-down.
Heel lancing	Central line insertion/removal	Urethral catheterisation or MCU
Lumbar puncture	Chest drain insertion/removal	Laceration repair.
Retinopathy of prematurity examination	Chest physiotherapy	Joint manipulation.
Suprapubic bladder tap	Dressing change	Burns and other wound dressing.
Venipuncture	Gavage tube insertion	Bone marrow aspiration.
Eye examination	Intramuscular injection	Joint aspiration and/or injection. Renal biopsy.
	Laser therapy for retinopathy	Radiological imaging (MRI, CT).
	Peripheral venous catheterization
	Mechanical ventilation
	Postural drainage
	Removal of adhesive tape
	Suture removal
	Tracheal intubation/extubation
	Ventricular tap

Table 8

General Principles in Pain Management in a Surgical Neonate

Pain in newborns is often unrecognised and undertreated. Neonates do feel pain, and analgesia should be prescribed when indicated during medical care. Procedures painful in adults should be considered painful in newborns, even if they are preterm.

The appropriate use of environmental, behavioral and pharmacological interventions can prevent, reduce or eliminate neonatal pain in many clinical situations.

Sedation does not provide pain relief and may mask the neonate's response to pain.

Clinical units providing health care to newborns should develop written guidelines and protocols for the management of neonatal pain.

A lack of behavioral responses (including crying and movement) does not necessarily indicate a lack of pain.

Pharmacological therapy when indicated with appropriate safe dosage by using computer generated medication doses

Intra muscular injections Drugs should be administered intravenously whenever possible. EMLA (0.5–1.0g) should be applied over desired site, 60–90 minutes prior. Oral sucrose, holding, swaddling or containment by flexing and holding should be employed with multisensory stimulation. Vitamin K is preferably administered by intramuscular route soon after birth for which most centers donot use oral sucrose or EMLA (68,69,79).

Nasogastric or orogastric tube insertion Oral sucrose should be used whenever possible immediately prior to the procedure. Holding, swaddling or containment by flexing and holding, employ multisensory stimulation should continue during the procedure. Insertion should be gentle coupled with adequate lubrication and optimal positioning with head in neutral or “sniffing position”, inserting the tube in vertical direction at right angles to the face (68,69,79).

Arterial puncture, percutaneous venous catheter insertion, percutaneous arterial catheter insertion, peripheral arterial/venous cut down/central cannula At the proposed site EMLA (0.5–1.0g) should be applied 60–90 minutes prior. Oral sucrose and containment by holding should be considered throughout the procedure. Opioid can be given, if intravenous access is available. Subcutaneous infiltration of lignocaine for arterial cannulation or cutdowns^. is a satisfactory practice (67,80–88).

Lumbar puncture EMLA cream (0.5–1.0g) should be applied 60–90 minutes prior at proposed site. Consider oral sucrose as above and containment by holding. Opioid can be administered if intravenous access is available. Consider subcutaneous infiltration of lignocaine whenever possible (67–69,80–86).

Endotracheal intubation: Tracheal intubation without the use of analgesia or sedation should be performed only for resuscitation/life threatening situations with nonavailability of intravenous line. When performing intubation outside operation theatre setting, atropine, morphine, or fentanyl, thiopental sodium and nondepolarizing or depolarizing muscle relaxant can be used in various combinations. Atropine and Ketamine can also be tried in some situations (45,46,86–91).

Endotracheal suction: It is considered a painful procedure, which can evoke stress response similar to other painful procedures. Oral sucrose as above and containment by holding need to be practiced throughout the procedure. Consider intravenous opioid whenever possible (68,69,80,81).

Chest tube insertion Anticipate the need for intubation and ventilation in neonates breathing spontaneously. Consider oral sucrose, containment and subcutaneous infiltration of lignocaine, slow opioid infusion whenever possible. Intravenous midazolam is not recommended. Short acting anaesthetics may be used (or nitrous oxide) (45,46,86–91).

Laser therapy for retinopathy of prematurity General anaesthesia is preferred. For neonates breathing spontaneously consider oral sucrose, containment and intravenous opioid is beneficial. Use of midazolam is not advisable. Other approaches include short acting anaesthetics (86,87). Acetaminophen given for postoperative pain has been shown to yield good results (91–93).

Circumcision The indications for circumcision usually occur beyond neonatal period, general anaesthesia is preferred for the same.

MRI/CT scans Children need to lie completely still for several minutes at a time in a noisy confined space. Suggested techniques: Infants less than 3 months miss a feed and then are fed just before the scan. Insert intravenous cannula just before feed. Use swaddling or containment in infants (59,98,99).

Urethral catheterisation or MCU Consider use of a pacifier with sucrose in neonates with use of swaddling and containment of infants. Use of nitrous oxide (with fasting precautions) can be considered as an alternative (59,96,97).

Joint manipulation and renal biopsy General anaesthesia or conscious sedation should be preferred. EMLA may be applied prior to needling. Nitrous oxide and ketamine may be used under appropriate monitoring.

Herniotomy This is a commonly performed surgical procedure for preterm and full term newborns. General anesthesia is combined with caudal epidural, ilioinguinal and ilioinguinal nerve blocks, and acetaminophen suppositories to reduce the amount of anesthetic and opioid required.

Pain management strategies for major surgical procedures have been discussed under section on regional analgesia.

Even with increasing awareness regarding management of pain in the newborns and availability of published guidelines for the same, the newborns continue to experience pain. Studies have shown that only a third of patients undergoing painful procedures in the NICU receive appropriate analgesic therapy (99,100). There is phenomenal work in last two decades on neonatal pain and its consequences but there is lack of its uniform application. Ongoing research into identifying optimal medication, dosing regimens and there long term effects is crucial. Evidence based treatment guidelines should be followed.

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