Regional analgesia in neonates undergoing thoracoabdominal surgeries: A pilot study

Abstract

OBJECTIVE:

The primary aim of this pilot study was to assess feasibility and to evaluate if peri-operative pain management with regional analgesia resulted in decreased use of narcotic medication and earlier return to preoperative respiratory/nutritional status.

STUDY DESIGN:

Cases were defined as infants who received regional analgesia as part of their perioperative anesthetic management. Controls were matched for surgical procedures without regional analgesia.

RESULTS:

Fifteen cases were identified and matched with 17 controls. Infants undergoing inguinal hernia repair returned to baseline earlier and were not intubated. There was no difference in time to extubation in other thoracoabdominal surgeries. There was no difference in cumulative narcotic analgesia administered between the two groups.

CONCLUSION:

Postoperative regional analgesia is feasible in neonates. Inguinal hernia repair with regional anesthesia was performed without intubation and returned to preoperative status earlier. No differences were observed with other surgeries. Further prospective, randomized, multicenter studies are needed.

1 Introduction

Treatment of pain in the neonate has come a long way since early attitudes that infants were not capable of experiencing pain. It is now known that adequate pain control is necessary and humane in the care of newborn infants in the neonatal intensive care unit (NICU) [1, 2]. Pain related stress in the preterm neonate can lead to pain sensitization in childhood as well as impact emotional and neurocognitive outcome [3, 4]. However, narcotic analgesia to provide comfort during ventilation and to treat postoperative pain can lead to dependence and may be associated with abnormal neurodevelopmental outcome [5 –7]. Current research efforts are evaluating ways to mitigate pain burden without impairing long-term neurocognitive and emotional development. One approach to providing analgesia without risking narcotic dependence is to use regional analgesia.

The three major types of regional analgesic techniques used in neonatal population are listed below.

The thoracic paravertebral block (TPVB) is a nerve block that in many situations can replace an epidural. Contained within the paravertebral space are the spinal nerve roots which are invested by and continuous with the dural sleeve of the spinal canal, as well as the sympathetic chain.

The transverse abdominis plane (TAP) block is a peripheral nerve block designed to anesthetize the nerves supplying the anterior abdominal wall (T6 to L1)

Continuous caudal anesthesia usually employed in cases of inguinal hernia repair

The primary aim for this pilot cohort observational study in infants undergoing thoracic or abdominal surgery, was to check feasibility and to assess whether peri-operative pain management with regional analgesia resulted decreased use of narcotic medication for pain control, and whether regional analgesia resulted in earlier return to baseline.

2 Methods

The Children and Youth Institutional review board at University at Buffalo approved this pilot study as quality improvement project with waiver for individual parental consent. Surgical and anesthesia consents were obtained as per hospital protocol. During the 12 month study period, three-way communication between neonatology, surgery, and anesthesiology occurred preoperatively, and plan for postoperative pain management was discussed. We matched cases that received regional analgesia with concurrent controls within the same twelve-month period (April 2016- June 2017). There were no matched controls for two patients within the study period - one patient with esophageal atresia/fistula (EA/TEF) and one with major abdominal surgery; we used historical matched controls from the previous 24-month epoch (January 2012-December 2014) for these two patients. Data were collected on prospective cases until discharge from NICU, or 30 days from day of surgery whichever occurred earlier. Total dose of narcotics was calculated intra and post operatively until criteria were met for “return to baseline”. Return to baseline was defined as time taken after surgery to get back to preoperative respiratory and nutritional status. Fentanyl dosage was converted to morphine equivalent by using 1:80 ratio as conversion factor [8, 9]. Only patients undergoing thoracic or abdominal surgery were included in the study. Subjects on chronic fentanyl therapy or on morphine for narcotic dependence prior to surgery were excluded.

Fig.1

Cases and controls surgical categories.

2.1 Regional analgesia techniques

“Awake” Continuous Caudal Anesthesia for inguinal hernia cases: Moderate sedation was used for placement of continuous caudal catheter. One infant required only a single dose of midazolam for caudal placement. The other 4 required midazolam and Propofol 1 mg/kg boluses for sedation during catheter placement. After positioning the infant in the lateral decubitus position, an 18 gauge angiocath was used to gain access to the caudal space under aseptic precautions. Lidocaine 2% with epinephrine or bupivacaine 0.25% with epinephrine was used for confirmation of placement and as a test dose (approximately 1 ml) was administered. A 20 gauge neuraxial catheter was then threaded approximately 2 cm past the tip of the angiocath and secured in place with a sterile dressing. Catheter was removed at the end of surgery. Surgical level of anesthesia was induced and maintained with 0.5–1 ml/kg boluses of 3% 2-chloroprocaine. In some cases, the local anesthetic (3% 2-chloroprocaine) was placed on a syringe pump at 1.5 ml/kg/h with top-off boluses of 0.5 ml/kg as needed.

Thoracic paravertebral block for EA/TEF cases: At the conclusion of surgery with the infant still in the lateral position, and before final dressings were applied, a TPVB catheter was inserted under real-time ultrasound guidance. The predominant approach was sagittal in-plane with needle passing from inferior to superior, and denting of the pleura sought for with approximately 1 ml of local anesthetic solution. After successful placement of needle tip, a 20 gauge peripheral block catheter was inserted approximately 1 cm past the tip of the needle. The catheter was then secured with liquid adhesive and opaque dressing separate from the surgical dressing.

Major abdominal surgery including exploratory laparotomy: All cases but one were managed with thoracic epidural analgesia placed during anesthesia induction. When the approach was thoracic level, then contrast fluoroscopy was used to confirm catheter placement, and spread of injectate. When the catheter was placed caudally and threaded up to the thoracic level, the distance was measured, but catheter location was not confirmed with ultrasound or fluoroscopy. In most cases the epidural was loaded before surgical incision with bupivacaine, and an infusion of 1.5% 2-chloroprocaine was used postoperatively until removal of the catheter.

Minimal bowel surgery, ostomy take-downs: With limited surgical dissection and lower expected levels of postoperative pain, ostomy take-down cases were managed with single shot TAP blocks supplementing general endotracheal anesthesia. If the ostomy incision was in the upper quadrant of the abdomen an ultrasound guided subcostal TAP block was placed. If the ostomy incision was midline or in the lower quadrant, then a combination of rectus sheath and/or classic ultrasound guided TAP blocks were placed.

Table 1
Demographics of cases and control

Comparison of demographics

All Cases All Controls Inguinal hernia Major abdominal surgeries Esophageal atresia/Fistula Ostomy take downs

Cases Controls Cases Controls Cases Controls Cases Controls

n 15 17 (5) (6) (5) (6) (3) (3) (2) (2)

Gestation (Weeks) 32 (6) 30 (5) 27 (3) 26.7 (3) 32 (7) 37 (0.5) 32 (2) 38 (1.5)^* 31 (10) 26 (3)

Corrected Gestation on surgery day (Weeks) 37 (2) 37 (3) 38 (0.8) 37.6 (3) 39 (4) 37 (0.5) 34 (2) 38 (1)^* 38.5 (2) 37

Birth weight (Kg) 2 (1) 1.7 (1) 0.9 (0.3) 1.0 (0.5) 2.3 (1.4) 3 (0.5) 1.7 (0.4) 2.8 (0.8)^* 2 (1.5) 1 (0.4)

Weight on surgery day (Kg) 2.9 (0.8) 2.7 (0.7) 3 (0.5) 3 (1) 2.7 (1) 3 (0.5) 2.1 (0.2) 2.8 (0.8) 2.6 (1) 2.1 (0.6)

Post natal age on surgery day 38 (47) 50 (40) 85 (19) 83 (42) 31 (46) 2 (0.5) 25 (20) 2 (0) 51 (53) 70 (33)

Males 9 15 5 6 1 4 1 3 2 2

Females 6 2 4 2 2

Preoperative respiratory support (n)

Mechanical Ventilation 1 0 1

Non Invasive^$ 3 3 3 1 1 1

Low Flow/Room air 11 14 2 6 5 5 2 2 2 1

Severity of BPD^Φ (n)

Mild 4 5 2 4 2 1

Moderate 1 2 1 2 0 0

Severe 3 1 3 1 1

Comparison of demographics
Gestation (Weeks)	32 (6)	30 (5)	27 (3)	26.7 (3)	32 (7)	37 (0.5)	32 (2)	38 (1.5)^*	31 (10)	26 (3)
Corrected Gestation on surgery day (Weeks)	37 (2)	37 (3)	38 (0.8)	37.6 (3)	39 (4)	37 (0.5)	34 (2)	38 (1)^*	38.5 (2)	37
Birth weight (Kg)	2 (1)	1.7 (1)	0.9 (0.3)	1.0 (0.5)	2.3 (1.4)	3 (0.5)	1.7 (0.4)	2.8 (0.8)^*	2 (1.5)	1 (0.4)
Weight on surgery day (Kg)	2.9 (0.8)	2.7 (0.7)	3 (0.5)	3 (1)	2.7 (1)	3 (0.5)	2.1 (0.2)	2.8 (0.8)	2.6 (1)	2.1 (0.6)
Post natal age on surgery day	38 (47)	50 (40)	85 (19)	83 (42)	31 (46)	2 (0.5)	25 (20)	2 (0)	51 (53)	70 (33)
Males	9	15	5	6	1	4	1	3	2	2
Females	6	2			4	2	2
Preoperative respiratory support (n)
Mechanical Ventilation	1	0					1
Non Invasive^$	3	3	3			1		1		1
Low Flow/Room air	11	14	2	6	5	5	2	2	2	1
Severity of BPD^Φ (n)
Mild	4	5	2	4	2	1
Moderate	1	2	1	2			0		0
Severe	3	1	3		1	1

^$Non-invasive –High flow nasal cannula, CPAP or Non-invasive positive pressure ventilation. ^ΦBronchopulmonary dysplasia definition based on NIH consensus conference, 2001. ^*P-Value <0.05 (unpaired T-test). Mean (SD).

Table 2

Regional analgesia types and other characteristics

Cases, n = 15
Surgical Diagnosis (n)	Medication used	Regional anesthesia(RA) type	Days with catheter in place	Adverse events
Inguinal Hernia(IH) (5)	chloroprocaine 3%	Intra-op Continuous Caudal	Intra-op only caudal	None
Major abdominal surgeries (5) Mean (SD)	chloroprocaine 1.5%	4 Thoracic Epidurals and 1 Subcostal peripheral nerve block	3.4 (0.5)	Abdominal distension and Suspected infection in 2 patients
Esophageal Atresia/fistula(EA) (3) Mean (SD)	chloroprocaine 1.5%	Thoracic Paravertebral Block Catheter	5 (0.5)	None
Ostomy Take downs (2)	bupivacaine 0.125%	Single Shot TAP*		Catheter leak

*TAP –Transversus abdominis plane.

Mean (SD).

Fig.2

Postoperative care comparison of Inguinal hernia(IH) cases and controls.

Table 3

Comparison of postoperative care data

Comparison of postoperative care
	All Cases	All Controls	Inguinal hernia		Major abdominal surgeries		Esophageal Atresia/fistula		Ostomy take downs
			Cases	Controls	Cases	Controls	Cases	Controls	Cases	Controls
N	15	17	(5)	(6)	(5)	(6)	(3)	(3)	(2)	(2)
Days intubated	1.3 (1.4)	2 (2.7)	0 (0)*	1 (0.2)	1.5 (0.7)	1.6 (0.5)	3.6 (0.5)	6 (5)	1 (0)	1 (1.4)
Feed start day	2.8 (3.1)	4.3 (4.2)	0.5 (0.8)	0.5 (0.5)	7.3 (3.5)	6.5 (3.2)	3 (1.7)	8.6 (5)	1.5 (0.7)	2 (2.8)
Full feed day	7.6 (8)	9 (7.5)	1.4 (3.3)	1.4 (0.9)	13.6 (3)	12 (3.8)	13 (12)	16 (8.5)	5.5 (3.5)	11 (7)
Back to Baseline	2.8 (3.2)	4 (3.8)	0.2 (0.4) *	1.2 (0.8)	7.3 (3)	6.5 (3.2)	3.6 (0.5)	6 (5)	1.5 (0.7)	2 (2.8)
Narcotic days^#	3.6 (2.9)	3.2 (3.7)	2 (1.7)	0.8 (0.7)	4.8 (3.7)	3.3 (2.4)	5.3 (2)	9.3 (4)	2.5 (3.5)	1 (1.4)
Acetaminophen days	1.5 (1.5)	1 (1)	3.2 (1.3)*	0.8 (1)	0.4 (0.8)	1.3 (1.6)	0.6 (1)	0.6 (1)	1.5 (2.1)	0 (0)
Acetaminophen dose^F	148 (190)	79 (180)	288 (230)	63 (87)	90 (180)	133 (289)	56 (96)	75 (129)	122 (124)	0 (0)
ME post op/kg^¶	2 (2.5)	2.5 (3)	0.3 (0.3)*	0.1 (0.1)	3.27 (3.6)	0.7 (0.59)	3.5 (1.9)	5.1 (4.4)	0.006 (0.008)	0.3 (0.4)
Total ME/kg^†	1.2 (2.5)	2 (2.5)	0.42 (0.3)	0.18 (0.09)	3.6 (3.7)	1.7 (1.1)	3.9 (1.5)	5.6 (4.4)	0.38 (0.5)	0.63 (0.89)

^FPostoperative total dose in mg. ^¶Narcotic dose in terms of morphine equivalent (ME) (Fentanyl dosage was converted to morphine equivalent by using 1:80 ratio as conversion factor). ^†Total ME dose/kg combining intra-operative and postoperative dose. ^*P value < 0.05 (Unpaired T-test). ^#Narcotics days includes total number of days when morphine and fentanyl were given. Mean (SD).

2.2 Data collection

We collected basic demographic data, duration and type of respiratory and nutritional support and use of narcotic and non-narcotic analgesia.

2.3 Statistical analysis

Normally distributed continuous data were analyzed by unpaired ‘t’ test. All other data were evaluated by Fisher’s exact test or Mann-Whitney test as appropriate.

3 Results

3.1 Study infants

Data were collected on a cohort of 32 infants who underwent either thoracic or abdominal surgery. 15 infants who received regional analgesia were classified as “cases” and other 17 patients were labeled as controls (Fig. 1). Infants were grouped according to surgery type and complexity of surgical interventions into 4 categories (Table 1): inguinal hernia (IH) repair, major abdominal surgeries included intestinal resection or anastomotic laparotomy, esophageal atresia/fistula (EA/TEF) and ostomy take-down. Cases with EA/TEF had lower gestational age and birth weight compared to controls, but in all other categories demographics were similar between cases and controls (Table 1).

The surgical diagnosis, types, medications and duration of regional analgesia and adverse events are shown in Table 2.

3.2 Inguinal hernia

Five infants underwent hernia repair with continuous caudal infusion of 3% 2-chloroprocaine for surgical anesthesia. Although most received some intraoperative sedation, cases did not need intubation, or conversion to general anesthesia, and returned to baseline on the same day. Post-operative pain was controlled with narcotics and acetaminophen (Fig. 2). Cases received more narcotics post-operatively in terms of morphine equivalent even though total narcotic exposure which included intra-op narcotic was similar in both groups (Table 3). All controls underwent repair under general anesthesia.

3.3 Major abdominal surgeries

There were a total of 5 cases and 6 controls. Postoperative course was similar in both groups in terms of days to extubation, initiation of fist feeds, and time to achieve full feeds. There was no difference in narcotic or acetaminophen use (Table 3).

3.4 Esophageal atresia/Fistula

There were 3 cases and 3 controls in this group. Postoperative course was similar in both groups (Table 3).

3.5 Diverting ostomy take downs

There were 2 cases and 2 controls during the study period and there were no differences between both groups (Table 3).

4 Discussion

Postoperative analgesia with regional anesthetic techniques is feasible in neonates. We did not demonstrate any difference in narcotic use or duration of intubation with the use of postoperative regional analgesia. The highlight of the study was that infants undergoing inguinal hernia surgery under caudal analgesia were able avoid intubation. Infants requiring inguinal hernia surgery in neonatal intensive care units are usually extremely premature with respiratory compromise secondary to bronchopulmonary dysplasia (BPD). These infants may take a long time to extubate after general anesthesia and surgery. By avoiding intubation and the effects of general anesthesia, cases with inguinal hernia returned to baseline much faster than controls. However, infants with inguinal hernia who underwent regional block received more narcotics and prolonged acetaminophen post operatively.

In this cohort of infants, we observed the effects of a real-world application of three regional analgesia techniques matched to thoracoabdominal surgeries. Our case numbers were low (15 cases). It is partly explained by the difficulty in acceptance of regional blocks placed due to widely varying surgeon and anesthesiologist preferences, and lack of effective preoperative communication and discussion of postoperative pain management. While we identified 35 cases where a block might be potentially indicated during the study period, we were only able to place them in 15 cases. The presence of abdominal erythema (and suspected infection) and catheter leak in one patient reduced the enthusiasm and support for these procedures in the NICU. Coordinated education of nurses and other caregivers on what is normal and what is concerning during assessment of infusion apparatus and catheter entry site is important. For instance, a modest amount of catheter leakage from entry site is expected because of the shallow depth of placement, but more than a reasonable amount may indicate catheter failure. Erythema from surgical causes or ostomy wound changes may not indicate need to remove an abdominal wall block catheter. As the hospital medical staff became acquainted and used to this novel pain management therapy and started seeing benefits of avoidance of intubation in some of these infants. Overall perception of medical staff during the course of the study improved as none of mentioned adverse events had any short or long term effects on health of these infants.

A Cochrane review of transversus abdominis plane (TAP) blocks for adult surgery found no significant differences [10]. In 2011, Jacobs et al. reported an audit of 11 infants and children receiving TAP blocks targeted to the level of incision and reported low pain scores and very little narcotic use, although this was not a comparative study trial, it is encouraging for the use of targeted TAP blocks for abdominal surgery [11]. Our study did not replicate these results probably due to the limitations listed below, but it is important note that 7 out of 11 patients in Jacobs et al study received routine intravenous acetaminophen infusion post-operatively. Such analgesic regimen was not part of post-operative pain management in our institution.

During this study period, the neonatal intensive care unit changed its pain scoring system from Neonatal Infant Pain Scale (NIPS) to CRIES (Crying, requires oxygen, Increased vital signs, Expression and Sleeplessness) Pain Scale. Nurses may have had a perception that infants not receiving general anesthesia may not have received adequate analgesia in the intra-operative period. We speculate that these two causes could have contributed to higher narcotic use post operatively in inguinal hernia patients. Inguinal hernia cases conducted under caudal anesthesia only did receive one intraoperative dose of morphine to blunt the onset of pain as the anesthetic effect was anticipated to recede in the early postoperative period. Standardizing anesthetic approach to include local analgesic/anesthetic infiltration by surgeon at conclusion of surgery, and/or adding a dose of long-acting local anesthetic through the caudal catheter before removal may decrease total narcotic dose.

There are major limitations to this pilot study. Small number of cases and heterogeneity of cases are major limitations. The implementation of a new pain scoring system during the study period may have had a considerable confounding effect on the administered cumulative doses of analgesic drugs. A larger study involving many centers using individual patient level randomization or cluster/NICU-based randomization with a cross-over design is needed to evaluate the role of regional anesthesia in neonates.

To conclude, the use of regional analgesia during postoperative care is feasible in the neonatal intensive care unit. Prospective, randomized trials for regional analgesia focusing on reduction of narcotic use during the postoperative period are warranted.

Conflict of interest

To the best of our knowledge, no conflict of interest, financial or other, exists

Footnotes

Acknowledgments

This study received support from Thomas Frawley fellowship at University at Buffalo (APS) and HD072929 (SL).

References

Bhalla

, Shepherd

, Tobias

. Neonatal pain management. Saudi J Anaesth. 2014;8(Suppl 1):S89–97.

Hall

, Anand

. Pain management in newborns. Clin Perinatol. 2014;41(4):895–924.

Doesburg

, Chau

, Cheung

, et al. Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age. Pain. 2013;154(10):1946–52.

Ranger

, Chau

, Garg

, et al. Neonatal pain-related stress predicts cortical thickness at age 7 years in children born very preterm. PLoS One. 2013;8(10):e76702.

Kesavan

. Neurodevelopmental Implications of Neonatal Pain and Morphine Exposure. Pediatr Ann. 2015;44(11):e260–4.

Schuurmans

, Benders

, Lemmers

, et al. Neonatal morphine in extremely and very preterm neonates: Its effect on the developing brain - a review. J Matern Fetal Neonatal Med. 2015;28(2):222–8.

Steinhorn

, McPherson

, Anderson

, et al. Neonatal morphine exposure in very preterm infants-cerebral development and outcomes. J Pediatr. 2015;166(5):1200–7.e4.

Berde

, Sethna

. Analgesics for the treatment of pain in children. N Engl J Med. 2002;347(14):1094–103.

Report

, Cancer pain relief and palliative care in children. 1998.

10.

Charlton

, Cyna

, Middleton

, et al. Perioperative transversus abdominis plane (TAP) blocks for analgesia after abdominal surgery. Cochrane Database Syst Rev. 2010(12):Cd007705.

11.

Jacobs

, Bergmans

, Arul

, et al. The transversus abdominis plane (TAP) block in neonates and infants - results of an audit. Paediatr Anaesth. 2011;21(10):1078–80.