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The effect of combined spinal-epidural anesthesia versus general anesthesia on the recovery time of intestinal function in young infants undergoing intestinal surgery: a randomized, prospective, controlled trial
Journal of Clinical Anesthesia (2012) 24, 439–445
Original Contribution
The effect of combined spinal-epidural anesthesia versus general anesthesia on the recovery time of intestinal function in young infants undergoing intestinal surgery: a randomized, prospective, controlled trial☆,☆☆ Mostafa Somri MD (Senior Lecturer)a,⁎, Ibrahim Matter MD (Lecturer)b , Constantinos A. Parisinos MD (Research Fellow)c , Ron Shaoul MD (Senior Lecturer)d , Jorge G. Mogilner MD (Professor) e , David Bader MD (Professor) f , Eldar Asphandiarov MD (Staff Anesthesiologist) a , Luis A. Gaitini MD (Professor) a a
Department of Anesthesiology, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel b Department of General Surgery, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel c Gastrointestinal Unit, Western General Hospital, Edinburgh EH4 2XU, UK d Pediatric Gastroenterology Unit, Rambam Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel e Pediatric Surgery Unit, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel f Neonatal Intensive Care Unit, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel Received 30 September 2011; revised 14 January 2012; accepted 14 February 2012
Keywords: Combined spinal-epidural anesthesia; Gastrointestinal function recovery; Infants; Intestinal surgery; Neonates
Abstract Study Objective: To assess the rate of restoration of gastrointestinal (GI) function following combined spinal-epidural (CSE) anesthesia compared with general anesthesia in young infants undergoing elective intestinal surgery. Design: Prospective, randomized, controlled study. Setting: Operating room and neonatal intensive care unit of a university hospital. Subjects: 50 young infants undergoing elective intestinal surgery. Interventions and Measurements: 50 young infants were randomly allocated to two groups of 25 patients each, a general anesthesia group and a CSE anesthesia group. The two groups were further divided into two subgroups according to whether the surgical procedure was performed on the small or
☆
Funded solely by internal department sources. The authors have no conflicts of interest to declare. ⁎ Correspondence: M. Somri, MD, Director of Pediatric Anesthesia Unit, Department of Anesthesia, Bnai Zion Medical Center, P.O.B 4940, 31048, Haifa, Israel. Tel.: +972 4 835 9346; fax: + 972 4 835 9821. E-mail address: [email protected] (M. Somri). ☆☆
0952-8180/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2012.02.004
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M. Somri et al. large intestine. The main outcome of this study was to measure the recovery times of GI function by determining the time to the first postoperative stool, duration of nasogastric feeding, and onset time of full enteral nutrition. The secondary outcome was to detect adverse events postoperatively. Main Results: Recovery of intestinal function was faster (P b 0.0001) and the frequencies of postoperative abdominal distension and pneumonia were less (P b 0.04) in infants who were anesthetized with CSE anesthesia than general anesthesia. Conclusions: Combined spinal-epidural anesthesia leads to faster restoration of GI function while reducing adverse events in infants who require elective intestinal surgery. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Postoperative ileus is a frequent unwanted complication in individuals who undergo gastrointestinal (GI) surgery. In young infants, postoperative ileus may result in abdominal distension, which contributes to significant postoperative morbidity, the need for assisted ventilation, and prolonged hospitalization [1]. Postoperative ileus is a part of a patient's stress response to intestinal surgery and its severity varies according to type of anesthesia, duration of the surgery, and intestinal pathology [2]. The underlying cause of postoperative ileus has been attributed to multiple mechanisms that reduce intestinal motility, particularly activation of spinal and local sympathetic reflexes and inflammatory mediators [2,3]. Most general anesthesia (GA) agents further contribute to morbidity after intestinal surgery by reducing gut motility [4,5]. The return of normal intestinal motility is faster in adult patients who undergo restorative proctocolectomy during thoracic epidural anesthesia than lumbar epidural anesthesia or GA alone [6,7]. A multimodal rehabilitation approach also has been tried as an alternative strategy for overcoming these unwanted postoperative intestinal consequences. This approach includes early feeding, early nasogastric tube removal, use of nonopioid analgesics, and intraoperative fluid restriction [1,8]. Combined spinal-epidural anesthesia (CSE) is an effective anesthetic technique which is used for elective major intestinal surgery in awake or sedated high-risk infants [9]. Spinal anesthesia provides conditions for performing the epidural block while the epidural component creates a stressfree surgical environment and enables extended postoperative analgesia. We undertook a randomized controlled study to test the hypothesis that GI function would occur earlier following CSE than GA in young infants who require either small or large intestinal surgery. We compared postoperative GI function recovery times after intestinal surgery in infants who were anesthetized with either CSE or GA as the primary outcome. We further compared the frequency of postoperative adverse events such as local or systemic infection, vomiting, diarrhea, and abdominal distension in the two patient groups as secondary outcome measures.
2. Material and methods 2.1. Study infants Ethical approval for this study was provided by the Ethical Committee of Bnai Zion Hospital, Haifa, Israel, and parental informed consent was obtained for each infant. Fifty premature, ex-premature, and full-term neonates who met the inclusion criteria were enrolled in the study, which was conducted between January 2005 and December 2009. Inclusion criteria were infants who required moderate to severe traumatic intestinal surgery; duodenoduodenostomy or duodenojejunostomy for duodenal atresia; ileocaecal resection for intestinal volvulus; ileostomy or colostomy closure for congenital anorectal malformations; and surgical repair of Hirschprung's disease. Exclusion criteria were infants with coagulopathy, sepsis, vertebral column malformations, and neurological diseases. Infants were also excluded if they required emergency bowel surgery, exploratory laparotomy, or had intestinal necrotizing enterocolitis.
2.2. Study groups and anesthesia Fifty infants were randomized preoperatively to two groups. Fifty envelopes, 25 containing odd and 25 containing even numbers obtained from a computer-generated table, were prepared and represented the GA or CSE group, respectively. The person responsible for data analysis was not involved in the randomization process. The two groups of infants were further divided into two subgroups according to whether the surgical procedure was done on the small or large intestine. General anesthesia group infants were induced with intravenous (IV) propofol (2-4 mg/kg) and fentanyl (2-4 μg/kg), and endotracheal intubation was facilitated by rocuronium bromide (0.5 mg/kg). Anesthesia was maintained using 0.5%-1% isoflurane in an air-oxygen mixture [attempting to maintain inspired oxygen concentration between 30% and 50%; however, the airoxygen mixture was modified in certain patients to maintain oxygen saturation (SpO2) ≥ 94% during surgery] and IV fentanyl, as needed. In the CSE group, patients were comforted by offering a pacifier dipped in 50% glucose solution; if a CSE group
CSE in young infants infant appeared anxious, a dose of 0.05 mg/kg of midazolam was administered during CSE. Combined spinal-epidural infants were induced by injecting preservative-free isobaric 0.5% bupivacaine (0.8 mg/kg) into the L4-L5 or L5-S1 interspaces using a 25-gauge (G) styletted needle (Becton Dickinson S.A, Madrid, Spain). After the onset of spinal anesthesia and using sterile conditions, sacral canal access was established through the sacrococcygeal membrane with an 18-G Crawford needle. A 20-G epidural catheter (B. Braun Medical, Inc. Melsungen, Germany) was advanced to the desired thoracic segments by measuring the distance from the sacral hiatus to the target thoracic segment on the infant's back, such that its tip was positioned between the desired T5 and T10 spinal segments. Correct catheter placement was confirmed by a portable epidurogram after filling the catheter with 0.5 mL of iohexol (Omnipaque® 300; Nycomed, Oslo, Norway). A test dose of 0.1 mL/kg of 1% lidocaine with 1:200,000 epinephrine was administered, and the resulting effects on heart rate (HR), blood pressure (BP), ST-segment amplitude, or arrhythmias were noted. The catheter was withdrawn and re-sited if HR was increased by ≥ 10 beats per minute (bpm); systolic blood pressure (SBP) increased by ≥ 15 mmHg above baseline; ST-segment changes occurred at an excess of 0.5 mV; or arrhythmias were detected. Since the effect of intrathecal bupivacaine is short, 0.5 mL/kg of 0.25% bupivacaine was injected into the epidural catheter 30 to 40 minutes after induction.
2.3. Assessment of CSE efficacy The efficacy of CSE was established by the absence of a) startling, b) crying, c) hind limb flexion withdrawal reflexes, d) arching of the torso, e) surges in BP, and f) a respiratory rate N than 20% above baseline values. The success of CSE was defined when a) lumbar puncture and access to the sacral canal was achieved within three attempts, b) the epidural catheter was correctly placed between the T5-T10 segments within two attempts, and c) anesthesia was adequate for surgery, obviating the need for additional systemic analgesia. When the infant was anxious but not in pain during surgery (ie, there was no change in vital signs ≥ 20% over preincision baseline), sedation was induced by administering IV midazolam at incremental doses of 0.05 mg/kg up to a maximal dose of 0.15 mg/kg. Whenever spinal anesthesia and/or insertion of the epidural catheter failed, CSE was immediately switched to GA with endotracheal intubation, and the infant was removed from the study.
441 monitor (Datex-Ohmeda, Inc., Madison, WI, USA). All GA infants were mechanically ventilated: peak inspiratory pressure was maintained between 18-30 cm H20, and endtidal CO2 (ETCO2) was maintained between 30 and 50 mmHg. Urine output of each infant was also measured every 30 minutes intraoperatively and postoperatively. Two peripheral IV catheters were inserted before the start of surgery for perioperative fluid management. Ringer's lactate and 5% glucose solutions were administered for intraoperative fluid maintenance at a rate of 4 mL/kg/hr. Additional Ringer's lactate was given for fluid replacement of third-space losses and blood loss. Packed red blood cells were transfused when infants bled ≥ 10% of their blood volume intraoperatively.
2.5. Postoperative patient management Following surgery, all infants were transferred to a neonatal intensive care unit (NICU), where monitoring of vital signs, urinary output, and mechanical ventilation if required, were continued. Blood samples were collected postoperatively in all infants for full blood count, plasma glucose, electrolytes, and assessment of venous or arterial blood gas measurements. The CRIES (C=crying, R=requires oxygen to keep SpO2 N 95%, I=increased vital signs, E=expression, S=sleeplessness) neonatal postoperative pain measurement score, which was carried out by the attending nurses every two hours, was used to assess severity and duration of postoperative pain. The attending nurses and physicians in the NICU [10] used values equal to or higher than 4 as scores requiring analgesic dose modification or technique change. Continuous IV fentanyl was administered in the GA group at a dose of 1-5 μg/kg/hr according to CRIES score. A continuous infusion of 0.1% bupivacaine at a rate of 0.2 mg/ kg/hr was given for up to 48 hours for postoperative analgesia in the CSE group. When the continuous epidural infusion was not efficacious, IV fentanyl at a rate of 1-5 μg/ kg/hr was given. The amount of fentanyl that was required for relief of postoperative pain control was recorded in both groups to determine the efficacy of postoperative analgesia and its probable effect on the GI recovery function. Early enteral feeding of all infants was started through a nasogastric tube, which had been inserted in all infants prior to surgery. Full feeding was defined as an infant's ability to tolerate at least 80% of daily maintenance volume [11]. In cases of abdominal distension or vomiting, all feeding was stopped until symptom resolution. The nasogastric tube was removed when bowel function was restored, ie, at passage of stools.
2.4. Intraoperative patient management 2.6. Outcome measurements Intraoperative arterial SBP, diastolic (DBP), mean arterial pressure (MAP), HR, SpO2, and body temperature of all infants were monitored continuously using an AS/3 Datex
The primary outcome, namely restoration of bowel function, was determined by recording the time to the first
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postoperative stool, duration of nasogastric feeding, and onset time of full enteral nutrition. Since the process of postoperative bowel recovery typically lasts between 3 and 5 days [3], times to the first postoperative stool were divided into early (b 5 days) and late (N 5 days). The secondary outcomes (frequency of postoperative adverse events such as vomiting, diarrhea, significant abdominal distension, local wound infection, urinary tract infection, and pneumonia) were recorded in the two study groups.
2.7. Statistical analysis Data were analyzed using a computerized statistical software program (SPSS v15.0; SPSS, Inc., Chicago, IL, USA). Study power was set at 80% to detect a 30% reduction in time to the first defecation. A sample size of 21 infants in each group, with a risk of 0.05, was required for the study. The indices used to measure recovery of GI function in the two study groups were compared by either an extended Chi-square test or Fisher's Exact test when the expected frequency was b 5. Differences in demographic data of the two study groups were analyzed by an independent Student's t-test. Changes in respiratory and hemodynamic parameters within the groups were analyzed by the Mann-Whitney U test. Repeated-measures analysis of variance was used to compare the differences between the cardiorespiratory parameters in the two study groups. Continuous variables are expressed as means ± standard deviation or medians and ranges. The level of significance was set at 0.05.
GA group and 16 infants in the CSE group were preterm infants and suffered from various pulmonary diseases such as bronchopulmonary dysplasia, neonatal respiratory distress syndrome, and apnea of prematurity. The remaining infants in both study groups were full-term newborns with no physical or medical comorbidities. Four infants were excluded from the final analysis. Two infants in the GA group were excluded from the study because each required unplanned additional procedures. Combined spinal-epidural anesthesia was unsuccessful in two infants: in one infant the epidural catheter could not be inserted, and the other infant required intraoperative mechanical ventilation due to insufficient sensory epidural block.
3.2. Intraoperative patient management In the CSE group, the onset of complete motor block occurred within 2 to 4 minutes and the onset of sensory block within 6 to 8 minutes after the spinal anesthesia. Placement of the epidural catheter was correct in all instances. The durations of the intestinal surgery in both study groups did not differ significantly [111 ± 61 min (GA group) vs 100 ± 32 min (CSE group)]. Furthermore, intraoperative MAP, HR, and SpO2 were maintained constant within normal ranges, with no significant differences seen within and between the two study groups before and during surgery (Table 2). Thirteen infants in the GA group and 15 infants in the CSE group required a homologous blood transfusion to maintain hemoglobin level above 11 g/dL.
3.3. Outcome measurements
3. Results 3.1. Study infants No significant differences were noted between the two groups in demographic data (Table 1). Fourteen infants in the
Table 1
Demographic data of the study group infants
Characteristics Post-conceptual age (wks) Age at time of surgery (wks) Birth weight (kg) Weight at time of surgery (kg) Gender (M/F)
GA group (N=23)
CSE group (N=23)
P-value
50.2 ± 6.4
48.1 ± 5.3
n.s
7.7 ± 2.1
8.0 ± 3.9
n.s
2.0 ± 0.9 2.9 ± 1.0
2.0 ± 0.9 2.7 ± 0.8
n.s n.s
12/11
13/10
n.s
Restoration of GI function was faster in the CSE group than the GA group. Specifically, almost all of the infants in the CSE group passed their first postoperative stool within 5 postoperative days, regardless of the site of GI surgery (Table 3). In contrast, most GA group infants took more than 5 days to pass their first postoperative stool (Table 3). The faster restoration of GI function in the CSE group was also evidenced when comparing the duration of nasogastric tube feeding and onset time of full enteral feeding of the two study groups (Table 4).
3.4. Frequency of postoperative adverse events
Data are means ± standard deviation. The GA group received general anesthesia, the CSEA group received combined spinal-epidural anesthesia.
Seven infants from the GA group required mechanical ventilation in the NICU due to preexisting pulmonary diseases or long duration of surgery (N 3 hrs). Three GA group infants developed episodes of pneumonia, two of whom were ventilated in the NICU. No CSE group patients developed pneumonia. More infants in the GA group than the CSE group developed postoperative abdominal distension and a trend for more episodes of pyrexia of unknown origin (Table 5). Although other adverse events, namely vomiting, diarrhea, local wound or urinary tract infections
CSE in young infants Table 2
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Comparison of intraoperative cardiorespiratory data between the two study groups (repeated measurements)
Cardiorespiratory variables MAP (mmHg) GA mean (SD) CSE mean (SD) HR (bpm) GA mean (SD) CSE mean (SD) SpO2 (mmHg) GA mean (SD) CSE mean (SD)
Baseline
20 min
40 min
60 min
End of surgery
P-value
55.4 (4.7) 53.2 (7.1)
54.3 (4.4) 52.2 (4.0)
52.9 (5.9) 51.5 (6.3)
52.3 (5.7) 54.6 (5.7)
56.5 (5.9) 54.3 (5.8)
0.353
147.9 (10.7) 146.7 (11.5)
148.4 (10.9) 149.2 (12.2)
140.6 (12.5) 142.5 (9.4)
140.3 (11.3) 144.4 (10.3)
140.7 (13.4) 145.3 (8.9)
0.390
96.5 (1.4) 96.4 (1.6)
96.2 (1.5) 96.4 (1.7)
95.9 (1.5) 96.9 (1.7)
96.2 (1.0) 96.7 (1.1)
96.4 (0.9) 96.4 (0.9)
0.147
Baseline=before intrathecal anesthesia, 20’=20 minutes after intrathecal anesthesia, 40’=40 minutes after epidural bupivacaine, 60’=during surgery, MAP=mean arterial pressure, GA=general anesthesia, CSE=combined spinal-epidural anesthesia, HR=heart rate; SpO2= oxygen saturation.
were similar in both study groups, when we compared all study patients who experienced at least one adverse event between the two groups, a higher difference was seen in the GA group (Table 5). Postoperatively, all patients from the GA group required a continuous fentanyl infusion in the NICU (range 60-3,000 μg, median infusion 250 μg). Twenty CSE patients were comfortable with continuous epidural bupivacaine analgesia for 48 hours and did not require additional IV doses of analgesics. Three CSE group patients required continuous IV fentanyl in the NICU according to the study protocol (range 10-200 μg, median 60 μg). Twenty patients from the CSE group required IV midazolam for sedation. Three patients received a maximum dose of 0.15 mg/kg, the rest were administered 2-4 doses of 0.05 mg/kg of midazolam, and all were easily aroused by minimal stimulation. No CSE group patient developed adverse systemic toxicity due to local anesthetic infusion either intraoperatively or postoperatively.
Table 3 Times to passing of first postoperative stool in the two study groups, and relationship of the event to the site of intestinal surgery Onset time of GI function (days)
Small intestine Large Intestine Overall
b 5 days
2
9
0.010
N 5 days
8
3
b 0.0001
2 11 4 19
10 1 19 4
b 0.0001
b N b N
5 days 5 days 5 days 5 days
GA group (N=23)
CSE group (N=23)
P-value
Site of surgery
The numbers in each group column = number of infants. GI=gastrointestinal. The GA group received general anesthesia, the CSE group received combined spinal-epidural anesthesia.
4. Discussion Recovery of intestinal function following intestinal surgery was faster, and the frequency of postoperative episodes of abdominal distension and pneumonia was lower, in infants who were anesthetized with CSE than GA. Information about the relationship between type of anesthesia and frequency of postoperative ileus in young infants is lacking. Results from various studies and one metaanalysis in the adult population showed that the duration of postoperative ileus was reduced and restoration of GI function was faster when intestinal surgery was performed in patients anesthetized using combined GA and thoracic epidural anesthesia versus GA alone [12-14]. Postoperative ileus occurs when the afferent limb of the spinal reflex arc is activated by any surgical procedure on the intestine, and the sympathetically mediated efferent limb responds by slowing the gut's propulsive activity to cause bowel distension and no passage of flatus and stool. Postoperative ileus is also caused by mechanical manipulations of the intestine and the duration of such manipulations, as well as inflammation, electrolyte imbalance, anemia, and ischemia of the bowel. All of the above influence the incidence, severity, and duration of postoperative ileus [1]. Some GA agents may contribute to morbidity after GI surgery, probably by diminishing intestinal perfusion and
Table 4 Comparison of markers of gastrointestinal recovery in the two study groups Parameters
GA group (N=23)
CSE group (N=23)
P-value
Duration of nasogastric tube feeding (days) Onset time of full enteral feeding (days)
7.1 ± 1.0
5.3 ± 0.9
0.0001
8.2 ± 2.2
5.2 ± 0.9
0.0001
Data are means ± standard deviation. The GA group received general anesthesia, the CSE group received combined spinal-epidural anesthesia.
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Table 5 Frequency of postoperative adverse events in the two study groups Adverse event
GA group CSE group P-value (N=23) (N=23)
Vomiting 3 Diarrhea 5 Abdominal distension 14 Wound infection 3 Pneumonia 3 Urinary tract infection 4 Pyrexia of unknown origin 6 Number of patients with 14 at least one event
2 6 7 3 0 1 1 7
1 0.73 0.038 0.6 0.038 0.34 0.097 0.038
The numbers in each group column = number of infants. The GA group general anesthesia, the CSE group received combined spinal-epidural anesthesia.
oxygen delivery [15], and opioid analgesics are well known for exerting a direct slowing action on gut motility [16]. The established positive effect of epidural local anesthetic on the reduced incidence and severity of postoperative ileus and the rapid recovery of intestinal function has been attributed to the segmental blockade of the visceral afferent and efferent pathways by the high thoracic application of local anesthetic for at least 48 hours and a concomitant increase in splanchnic blood flow [17,18]. Research on lumbar or low thoracic epidural administration of local anesthetics used in abdominal surgery has not shown any benefit of an epidural analgesic in reducing the frequency and duration of postoperative ileus [19]. In our study, the tips of the epidural catheters in the CSE group infants were placed in the high thoracic spinal segments (T5-T10) and continuous analgesia was maintained for 48 hours using only an infusion of a local anesthetic agent. Our results support the findings in adults in which the location of the epidural catheter is crucial for providing continuous analgesia. The direct passage of food into the gut lumen increases splanchnic blood flow and stimulates the gut's immune system [20]. Consequently, the likelihood of infection is minimized and the clinical outcome is improved. Prolonged fasting causes thinning of the intestinal mucosa accompanied by villous shortening and decreased enzymatic activity. The early postoperative feeding of infants with small volumes also improves enterocyte maturation, thereby preventing further intestinal atrophy [21,22]. We found a lower frequency of adverse events in CSE group infants than GA group infants, with fewer episodes of abdominal distension and pneumonia, and a trend toward fewer episodes of pyrexia of unknown origin. One possible reason for this reduced frequency of infection in the CSE infants was the early onset of full enteral feeding and its influences on the immune system. This possibility is supported by the results of previous studies [23,24]. Seven infants in the GA group required mechanical ventilation after surgery, whereas no infants in the CSE
group required postoperative respiratory support while in the NICU unit. Mechanical ventilation is a potential cause of pneumonia in infants with preexisting prematurity lung diseases [25]. We feel that this requirement accounted for the increased frequency of pneumonia in the GA group. The principal disadvantage of CSE is that it is timeconsuming to perform two blocks in small infants, and challenging to thread the catheters to the target spinal segment; in some cases during our study, the whole process lasted about 40 minutes. Other CSE disadvantages include the potential risk of airway compromise in a sedated child with an uncontrolled airway who is undergoing intestinal surgery. Precautions should focus on maintained patency of the infants’ airways during surgery. The limitation of this study was the fact that the epidural bolus and the distribution of the local anesthetic in the cerebrospinal fluid space may have caused a high spinal block [26]. However, we found no data about this issue in the pediatric regional anesthesia literature. In this study, injection of the epidural dose of bupivacaine occurred almost 40 minutes after the intrathecal injection (when most of the bupivacaine should have been metabolized). Another limitation of this study was that young infants have a lower concentration of albumin and alpha 1-acid glycoprotein, and the serum concentration was 50% lower in the premature neonates than the full-term neonates [27]. This fact may reduce protein binding of local anesthetics and result in a dramatic increase of the concentration of free bupivacaine, potentially predisposing infants to central nervous system toxicity. For this reason, the maximum bupivacaine infusion rate was limited to 0.2 - 0.25 mg/kg/hr for neonates and 0.5 mg/kg/hr for older infants, as suggested in previous studies [28-30]. This study showed that CSE in small infants enabled early recovery of intestinal function, diminished the need for intraoperative and postoperative opioid analgesia, and reduced the frequency of postoperative episodes of abdominal distension and pneumonia. In conclusion, CSE led to faster restoration of GI function and reduction of adverse events than GA in young infants who required elective intestinal surgery.
Acknowledgment The authors thank Dr. Arieh Bomzon for assistance in the preparation of this manuscript. Specific acknowledgment and thanks to Ilana Merhav, head librarian, Bnai Zion Medical Center.
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445 [17] Liu S, Carpenter RL, Mackey DC, et al. Effect of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology 1995; 83:757-65. [18] Steinbrook RA. Epidural anesthesia and gastrointestinal motility. Anesth Analg 1998;86:837-44. [19] Wallin G, Cassuto J, Högström S, Rimbäck G, Faxén A, Tollesson PO. Failure of epidural analgesia to prevent postoperative paralytic ileus. Anesthesiology 1986;65:292-7. [20] Braga M, Gianetti L, Gentilini O, Parisi V, Salis C, Di Carlo V. Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition. Crit Care Med 2001;29: 242-8. [21] Alpers DH. Enteral feeding and gut atrophy. Curr Opin Clin Nutr Metab Care 2002;5:679-83. [22] Dunn L, Hulman S, Weiner J, Kliegman R. Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial. J Pediatr 1988; 112:622-9. [23] Moore EE, Dunn EL, Jones TN. Immediate jejunostomy feeding. Its use after major abdominal trauma. Arch Surg 1981;116:681-4. [24] Beier-Holgersen R, Boesby S. Influence of postoperative enteral nutrition on postsurgical infections. Gut 1996;39:833-5. [25] Steward DJ. Preterm infants are more prone to complications following surgery than are term infants. Anesthesiology 1982;56: 304-6. [26] Ithnin F, Lim Y, Sia AT, et al. Combined spinal epidural causes higher level of block than equivalent single-shot spinal anesthesia in elective cesarean patients. Anesth Analg 2006;102:577-80. [27] Lerman J, Strong A, LeDez KM, Swartz J, Rieder MJ, Burrows FA. Effects of age on the serum concentration of alpha 1-acid glycoprotein and the binding of lidocaine in pediatric patients. Clin Pharmcol Ther 1989;46:219-25. [28] Berde CB. Convulsions associated with pediatric regional anesthesia. Anesth Analg 1992;75:164-6. [29] Bösenberg AT. Epidural analgesia for major neonatal surgery. Paediatr Anaesth 1998;8:479-83. [30] Sethna NF, Berde CB. Pediatric regional anesthesia. In: Gregory GA, editor. Pediatric anesthesia. 3rd ed. New York: Churchill Livingstone, Inc.; 1994. p. 281-317.
Original Contribution
The effect of combined spinal-epidural anesthesia versus general anesthesia on the recovery time of intestinal function in young infants undergoing intestinal surgery: a randomized, prospective, controlled trial☆,☆☆ Mostafa Somri MD (Senior Lecturer)a,⁎, Ibrahim Matter MD (Lecturer)b , Constantinos A. Parisinos MD (Research Fellow)c , Ron Shaoul MD (Senior Lecturer)d , Jorge G. Mogilner MD (Professor) e , David Bader MD (Professor) f , Eldar Asphandiarov MD (Staff Anesthesiologist) a , Luis A. Gaitini MD (Professor) a a
Department of Anesthesiology, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel b Department of General Surgery, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel c Gastrointestinal Unit, Western General Hospital, Edinburgh EH4 2XU, UK d Pediatric Gastroenterology Unit, Rambam Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel e Pediatric Surgery Unit, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel f Neonatal Intensive Care Unit, Bnai Zion Medical Center, the Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 32000, Israel Received 30 September 2011; revised 14 January 2012; accepted 14 February 2012
Keywords: Combined spinal-epidural anesthesia; Gastrointestinal function recovery; Infants; Intestinal surgery; Neonates
Abstract Study Objective: To assess the rate of restoration of gastrointestinal (GI) function following combined spinal-epidural (CSE) anesthesia compared with general anesthesia in young infants undergoing elective intestinal surgery. Design: Prospective, randomized, controlled study. Setting: Operating room and neonatal intensive care unit of a university hospital. Subjects: 50 young infants undergoing elective intestinal surgery. Interventions and Measurements: 50 young infants were randomly allocated to two groups of 25 patients each, a general anesthesia group and a CSE anesthesia group. The two groups were further divided into two subgroups according to whether the surgical procedure was performed on the small or
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Funded solely by internal department sources. The authors have no conflicts of interest to declare. ⁎ Correspondence: M. Somri, MD, Director of Pediatric Anesthesia Unit, Department of Anesthesia, Bnai Zion Medical Center, P.O.B 4940, 31048, Haifa, Israel. Tel.: +972 4 835 9346; fax: + 972 4 835 9821. E-mail address: [email protected] (M. Somri). ☆☆
0952-8180/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2012.02.004
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M. Somri et al. large intestine. The main outcome of this study was to measure the recovery times of GI function by determining the time to the first postoperative stool, duration of nasogastric feeding, and onset time of full enteral nutrition. The secondary outcome was to detect adverse events postoperatively. Main Results: Recovery of intestinal function was faster (P b 0.0001) and the frequencies of postoperative abdominal distension and pneumonia were less (P b 0.04) in infants who were anesthetized with CSE anesthesia than general anesthesia. Conclusions: Combined spinal-epidural anesthesia leads to faster restoration of GI function while reducing adverse events in infants who require elective intestinal surgery. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Postoperative ileus is a frequent unwanted complication in individuals who undergo gastrointestinal (GI) surgery. In young infants, postoperative ileus may result in abdominal distension, which contributes to significant postoperative morbidity, the need for assisted ventilation, and prolonged hospitalization [1]. Postoperative ileus is a part of a patient's stress response to intestinal surgery and its severity varies according to type of anesthesia, duration of the surgery, and intestinal pathology [2]. The underlying cause of postoperative ileus has been attributed to multiple mechanisms that reduce intestinal motility, particularly activation of spinal and local sympathetic reflexes and inflammatory mediators [2,3]. Most general anesthesia (GA) agents further contribute to morbidity after intestinal surgery by reducing gut motility [4,5]. The return of normal intestinal motility is faster in adult patients who undergo restorative proctocolectomy during thoracic epidural anesthesia than lumbar epidural anesthesia or GA alone [6,7]. A multimodal rehabilitation approach also has been tried as an alternative strategy for overcoming these unwanted postoperative intestinal consequences. This approach includes early feeding, early nasogastric tube removal, use of nonopioid analgesics, and intraoperative fluid restriction [1,8]. Combined spinal-epidural anesthesia (CSE) is an effective anesthetic technique which is used for elective major intestinal surgery in awake or sedated high-risk infants [9]. Spinal anesthesia provides conditions for performing the epidural block while the epidural component creates a stressfree surgical environment and enables extended postoperative analgesia. We undertook a randomized controlled study to test the hypothesis that GI function would occur earlier following CSE than GA in young infants who require either small or large intestinal surgery. We compared postoperative GI function recovery times after intestinal surgery in infants who were anesthetized with either CSE or GA as the primary outcome. We further compared the frequency of postoperative adverse events such as local or systemic infection, vomiting, diarrhea, and abdominal distension in the two patient groups as secondary outcome measures.
2. Material and methods 2.1. Study infants Ethical approval for this study was provided by the Ethical Committee of Bnai Zion Hospital, Haifa, Israel, and parental informed consent was obtained for each infant. Fifty premature, ex-premature, and full-term neonates who met the inclusion criteria were enrolled in the study, which was conducted between January 2005 and December 2009. Inclusion criteria were infants who required moderate to severe traumatic intestinal surgery; duodenoduodenostomy or duodenojejunostomy for duodenal atresia; ileocaecal resection for intestinal volvulus; ileostomy or colostomy closure for congenital anorectal malformations; and surgical repair of Hirschprung's disease. Exclusion criteria were infants with coagulopathy, sepsis, vertebral column malformations, and neurological diseases. Infants were also excluded if they required emergency bowel surgery, exploratory laparotomy, or had intestinal necrotizing enterocolitis.
2.2. Study groups and anesthesia Fifty infants were randomized preoperatively to two groups. Fifty envelopes, 25 containing odd and 25 containing even numbers obtained from a computer-generated table, were prepared and represented the GA or CSE group, respectively. The person responsible for data analysis was not involved in the randomization process. The two groups of infants were further divided into two subgroups according to whether the surgical procedure was done on the small or large intestine. General anesthesia group infants were induced with intravenous (IV) propofol (2-4 mg/kg) and fentanyl (2-4 μg/kg), and endotracheal intubation was facilitated by rocuronium bromide (0.5 mg/kg). Anesthesia was maintained using 0.5%-1% isoflurane in an air-oxygen mixture [attempting to maintain inspired oxygen concentration between 30% and 50%; however, the airoxygen mixture was modified in certain patients to maintain oxygen saturation (SpO2) ≥ 94% during surgery] and IV fentanyl, as needed. In the CSE group, patients were comforted by offering a pacifier dipped in 50% glucose solution; if a CSE group
CSE in young infants infant appeared anxious, a dose of 0.05 mg/kg of midazolam was administered during CSE. Combined spinal-epidural infants were induced by injecting preservative-free isobaric 0.5% bupivacaine (0.8 mg/kg) into the L4-L5 or L5-S1 interspaces using a 25-gauge (G) styletted needle (Becton Dickinson S.A, Madrid, Spain). After the onset of spinal anesthesia and using sterile conditions, sacral canal access was established through the sacrococcygeal membrane with an 18-G Crawford needle. A 20-G epidural catheter (B. Braun Medical, Inc. Melsungen, Germany) was advanced to the desired thoracic segments by measuring the distance from the sacral hiatus to the target thoracic segment on the infant's back, such that its tip was positioned between the desired T5 and T10 spinal segments. Correct catheter placement was confirmed by a portable epidurogram after filling the catheter with 0.5 mL of iohexol (Omnipaque® 300; Nycomed, Oslo, Norway). A test dose of 0.1 mL/kg of 1% lidocaine with 1:200,000 epinephrine was administered, and the resulting effects on heart rate (HR), blood pressure (BP), ST-segment amplitude, or arrhythmias were noted. The catheter was withdrawn and re-sited if HR was increased by ≥ 10 beats per minute (bpm); systolic blood pressure (SBP) increased by ≥ 15 mmHg above baseline; ST-segment changes occurred at an excess of 0.5 mV; or arrhythmias were detected. Since the effect of intrathecal bupivacaine is short, 0.5 mL/kg of 0.25% bupivacaine was injected into the epidural catheter 30 to 40 minutes after induction.
2.3. Assessment of CSE efficacy The efficacy of CSE was established by the absence of a) startling, b) crying, c) hind limb flexion withdrawal reflexes, d) arching of the torso, e) surges in BP, and f) a respiratory rate N than 20% above baseline values. The success of CSE was defined when a) lumbar puncture and access to the sacral canal was achieved within three attempts, b) the epidural catheter was correctly placed between the T5-T10 segments within two attempts, and c) anesthesia was adequate for surgery, obviating the need for additional systemic analgesia. When the infant was anxious but not in pain during surgery (ie, there was no change in vital signs ≥ 20% over preincision baseline), sedation was induced by administering IV midazolam at incremental doses of 0.05 mg/kg up to a maximal dose of 0.15 mg/kg. Whenever spinal anesthesia and/or insertion of the epidural catheter failed, CSE was immediately switched to GA with endotracheal intubation, and the infant was removed from the study.
441 monitor (Datex-Ohmeda, Inc., Madison, WI, USA). All GA infants were mechanically ventilated: peak inspiratory pressure was maintained between 18-30 cm H20, and endtidal CO2 (ETCO2) was maintained between 30 and 50 mmHg. Urine output of each infant was also measured every 30 minutes intraoperatively and postoperatively. Two peripheral IV catheters were inserted before the start of surgery for perioperative fluid management. Ringer's lactate and 5% glucose solutions were administered for intraoperative fluid maintenance at a rate of 4 mL/kg/hr. Additional Ringer's lactate was given for fluid replacement of third-space losses and blood loss. Packed red blood cells were transfused when infants bled ≥ 10% of their blood volume intraoperatively.
2.5. Postoperative patient management Following surgery, all infants were transferred to a neonatal intensive care unit (NICU), where monitoring of vital signs, urinary output, and mechanical ventilation if required, were continued. Blood samples were collected postoperatively in all infants for full blood count, plasma glucose, electrolytes, and assessment of venous or arterial blood gas measurements. The CRIES (C=crying, R=requires oxygen to keep SpO2 N 95%, I=increased vital signs, E=expression, S=sleeplessness) neonatal postoperative pain measurement score, which was carried out by the attending nurses every two hours, was used to assess severity and duration of postoperative pain. The attending nurses and physicians in the NICU [10] used values equal to or higher than 4 as scores requiring analgesic dose modification or technique change. Continuous IV fentanyl was administered in the GA group at a dose of 1-5 μg/kg/hr according to CRIES score. A continuous infusion of 0.1% bupivacaine at a rate of 0.2 mg/ kg/hr was given for up to 48 hours for postoperative analgesia in the CSE group. When the continuous epidural infusion was not efficacious, IV fentanyl at a rate of 1-5 μg/ kg/hr was given. The amount of fentanyl that was required for relief of postoperative pain control was recorded in both groups to determine the efficacy of postoperative analgesia and its probable effect on the GI recovery function. Early enteral feeding of all infants was started through a nasogastric tube, which had been inserted in all infants prior to surgery. Full feeding was defined as an infant's ability to tolerate at least 80% of daily maintenance volume [11]. In cases of abdominal distension or vomiting, all feeding was stopped until symptom resolution. The nasogastric tube was removed when bowel function was restored, ie, at passage of stools.
2.4. Intraoperative patient management 2.6. Outcome measurements Intraoperative arterial SBP, diastolic (DBP), mean arterial pressure (MAP), HR, SpO2, and body temperature of all infants were monitored continuously using an AS/3 Datex
The primary outcome, namely restoration of bowel function, was determined by recording the time to the first
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postoperative stool, duration of nasogastric feeding, and onset time of full enteral nutrition. Since the process of postoperative bowel recovery typically lasts between 3 and 5 days [3], times to the first postoperative stool were divided into early (b 5 days) and late (N 5 days). The secondary outcomes (frequency of postoperative adverse events such as vomiting, diarrhea, significant abdominal distension, local wound infection, urinary tract infection, and pneumonia) were recorded in the two study groups.
2.7. Statistical analysis Data were analyzed using a computerized statistical software program (SPSS v15.0; SPSS, Inc., Chicago, IL, USA). Study power was set at 80% to detect a 30% reduction in time to the first defecation. A sample size of 21 infants in each group, with a risk of 0.05, was required for the study. The indices used to measure recovery of GI function in the two study groups were compared by either an extended Chi-square test or Fisher's Exact test when the expected frequency was b 5. Differences in demographic data of the two study groups were analyzed by an independent Student's t-test. Changes in respiratory and hemodynamic parameters within the groups were analyzed by the Mann-Whitney U test. Repeated-measures analysis of variance was used to compare the differences between the cardiorespiratory parameters in the two study groups. Continuous variables are expressed as means ± standard deviation or medians and ranges. The level of significance was set at 0.05.
GA group and 16 infants in the CSE group were preterm infants and suffered from various pulmonary diseases such as bronchopulmonary dysplasia, neonatal respiratory distress syndrome, and apnea of prematurity. The remaining infants in both study groups were full-term newborns with no physical or medical comorbidities. Four infants were excluded from the final analysis. Two infants in the GA group were excluded from the study because each required unplanned additional procedures. Combined spinal-epidural anesthesia was unsuccessful in two infants: in one infant the epidural catheter could not be inserted, and the other infant required intraoperative mechanical ventilation due to insufficient sensory epidural block.
3.2. Intraoperative patient management In the CSE group, the onset of complete motor block occurred within 2 to 4 minutes and the onset of sensory block within 6 to 8 minutes after the spinal anesthesia. Placement of the epidural catheter was correct in all instances. The durations of the intestinal surgery in both study groups did not differ significantly [111 ± 61 min (GA group) vs 100 ± 32 min (CSE group)]. Furthermore, intraoperative MAP, HR, and SpO2 were maintained constant within normal ranges, with no significant differences seen within and between the two study groups before and during surgery (Table 2). Thirteen infants in the GA group and 15 infants in the CSE group required a homologous blood transfusion to maintain hemoglobin level above 11 g/dL.
3.3. Outcome measurements
3. Results 3.1. Study infants No significant differences were noted between the two groups in demographic data (Table 1). Fourteen infants in the
Table 1
Demographic data of the study group infants
Characteristics Post-conceptual age (wks) Age at time of surgery (wks) Birth weight (kg) Weight at time of surgery (kg) Gender (M/F)
GA group (N=23)
CSE group (N=23)
P-value
50.2 ± 6.4
48.1 ± 5.3
n.s
7.7 ± 2.1
8.0 ± 3.9
n.s
2.0 ± 0.9 2.9 ± 1.0
2.0 ± 0.9 2.7 ± 0.8
n.s n.s
12/11
13/10
n.s
Restoration of GI function was faster in the CSE group than the GA group. Specifically, almost all of the infants in the CSE group passed their first postoperative stool within 5 postoperative days, regardless of the site of GI surgery (Table 3). In contrast, most GA group infants took more than 5 days to pass their first postoperative stool (Table 3). The faster restoration of GI function in the CSE group was also evidenced when comparing the duration of nasogastric tube feeding and onset time of full enteral feeding of the two study groups (Table 4).
3.4. Frequency of postoperative adverse events
Data are means ± standard deviation. The GA group received general anesthesia, the CSEA group received combined spinal-epidural anesthesia.
Seven infants from the GA group required mechanical ventilation in the NICU due to preexisting pulmonary diseases or long duration of surgery (N 3 hrs). Three GA group infants developed episodes of pneumonia, two of whom were ventilated in the NICU. No CSE group patients developed pneumonia. More infants in the GA group than the CSE group developed postoperative abdominal distension and a trend for more episodes of pyrexia of unknown origin (Table 5). Although other adverse events, namely vomiting, diarrhea, local wound or urinary tract infections
CSE in young infants Table 2
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Comparison of intraoperative cardiorespiratory data between the two study groups (repeated measurements)
Cardiorespiratory variables MAP (mmHg) GA mean (SD) CSE mean (SD) HR (bpm) GA mean (SD) CSE mean (SD) SpO2 (mmHg) GA mean (SD) CSE mean (SD)
Baseline
20 min
40 min
60 min
End of surgery
P-value
55.4 (4.7) 53.2 (7.1)
54.3 (4.4) 52.2 (4.0)
52.9 (5.9) 51.5 (6.3)
52.3 (5.7) 54.6 (5.7)
56.5 (5.9) 54.3 (5.8)
0.353
147.9 (10.7) 146.7 (11.5)
148.4 (10.9) 149.2 (12.2)
140.6 (12.5) 142.5 (9.4)
140.3 (11.3) 144.4 (10.3)
140.7 (13.4) 145.3 (8.9)
0.390
96.5 (1.4) 96.4 (1.6)
96.2 (1.5) 96.4 (1.7)
95.9 (1.5) 96.9 (1.7)
96.2 (1.0) 96.7 (1.1)
96.4 (0.9) 96.4 (0.9)
0.147
Baseline=before intrathecal anesthesia, 20’=20 minutes after intrathecal anesthesia, 40’=40 minutes after epidural bupivacaine, 60’=during surgery, MAP=mean arterial pressure, GA=general anesthesia, CSE=combined spinal-epidural anesthesia, HR=heart rate; SpO2= oxygen saturation.
were similar in both study groups, when we compared all study patients who experienced at least one adverse event between the two groups, a higher difference was seen in the GA group (Table 5). Postoperatively, all patients from the GA group required a continuous fentanyl infusion in the NICU (range 60-3,000 μg, median infusion 250 μg). Twenty CSE patients were comfortable with continuous epidural bupivacaine analgesia for 48 hours and did not require additional IV doses of analgesics. Three CSE group patients required continuous IV fentanyl in the NICU according to the study protocol (range 10-200 μg, median 60 μg). Twenty patients from the CSE group required IV midazolam for sedation. Three patients received a maximum dose of 0.15 mg/kg, the rest were administered 2-4 doses of 0.05 mg/kg of midazolam, and all were easily aroused by minimal stimulation. No CSE group patient developed adverse systemic toxicity due to local anesthetic infusion either intraoperatively or postoperatively.
Table 3 Times to passing of first postoperative stool in the two study groups, and relationship of the event to the site of intestinal surgery Onset time of GI function (days)
Small intestine Large Intestine Overall
b 5 days
2
9
0.010
N 5 days
8
3
b 0.0001
2 11 4 19
10 1 19 4
b 0.0001
b N b N
5 days 5 days 5 days 5 days
GA group (N=23)
CSE group (N=23)
P-value
Site of surgery
The numbers in each group column = number of infants. GI=gastrointestinal. The GA group received general anesthesia, the CSE group received combined spinal-epidural anesthesia.
4. Discussion Recovery of intestinal function following intestinal surgery was faster, and the frequency of postoperative episodes of abdominal distension and pneumonia was lower, in infants who were anesthetized with CSE than GA. Information about the relationship between type of anesthesia and frequency of postoperative ileus in young infants is lacking. Results from various studies and one metaanalysis in the adult population showed that the duration of postoperative ileus was reduced and restoration of GI function was faster when intestinal surgery was performed in patients anesthetized using combined GA and thoracic epidural anesthesia versus GA alone [12-14]. Postoperative ileus occurs when the afferent limb of the spinal reflex arc is activated by any surgical procedure on the intestine, and the sympathetically mediated efferent limb responds by slowing the gut's propulsive activity to cause bowel distension and no passage of flatus and stool. Postoperative ileus is also caused by mechanical manipulations of the intestine and the duration of such manipulations, as well as inflammation, electrolyte imbalance, anemia, and ischemia of the bowel. All of the above influence the incidence, severity, and duration of postoperative ileus [1]. Some GA agents may contribute to morbidity after GI surgery, probably by diminishing intestinal perfusion and
Table 4 Comparison of markers of gastrointestinal recovery in the two study groups Parameters
GA group (N=23)
CSE group (N=23)
P-value
Duration of nasogastric tube feeding (days) Onset time of full enteral feeding (days)
7.1 ± 1.0
5.3 ± 0.9
0.0001
8.2 ± 2.2
5.2 ± 0.9
0.0001
Data are means ± standard deviation. The GA group received general anesthesia, the CSE group received combined spinal-epidural anesthesia.
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Table 5 Frequency of postoperative adverse events in the two study groups Adverse event
GA group CSE group P-value (N=23) (N=23)
Vomiting 3 Diarrhea 5 Abdominal distension 14 Wound infection 3 Pneumonia 3 Urinary tract infection 4 Pyrexia of unknown origin 6 Number of patients with 14 at least one event
2 6 7 3 0 1 1 7
1 0.73 0.038 0.6 0.038 0.34 0.097 0.038
The numbers in each group column = number of infants. The GA group general anesthesia, the CSE group received combined spinal-epidural anesthesia.
oxygen delivery [15], and opioid analgesics are well known for exerting a direct slowing action on gut motility [16]. The established positive effect of epidural local anesthetic on the reduced incidence and severity of postoperative ileus and the rapid recovery of intestinal function has been attributed to the segmental blockade of the visceral afferent and efferent pathways by the high thoracic application of local anesthetic for at least 48 hours and a concomitant increase in splanchnic blood flow [17,18]. Research on lumbar or low thoracic epidural administration of local anesthetics used in abdominal surgery has not shown any benefit of an epidural analgesic in reducing the frequency and duration of postoperative ileus [19]. In our study, the tips of the epidural catheters in the CSE group infants were placed in the high thoracic spinal segments (T5-T10) and continuous analgesia was maintained for 48 hours using only an infusion of a local anesthetic agent. Our results support the findings in adults in which the location of the epidural catheter is crucial for providing continuous analgesia. The direct passage of food into the gut lumen increases splanchnic blood flow and stimulates the gut's immune system [20]. Consequently, the likelihood of infection is minimized and the clinical outcome is improved. Prolonged fasting causes thinning of the intestinal mucosa accompanied by villous shortening and decreased enzymatic activity. The early postoperative feeding of infants with small volumes also improves enterocyte maturation, thereby preventing further intestinal atrophy [21,22]. We found a lower frequency of adverse events in CSE group infants than GA group infants, with fewer episodes of abdominal distension and pneumonia, and a trend toward fewer episodes of pyrexia of unknown origin. One possible reason for this reduced frequency of infection in the CSE infants was the early onset of full enteral feeding and its influences on the immune system. This possibility is supported by the results of previous studies [23,24]. Seven infants in the GA group required mechanical ventilation after surgery, whereas no infants in the CSE
group required postoperative respiratory support while in the NICU unit. Mechanical ventilation is a potential cause of pneumonia in infants with preexisting prematurity lung diseases [25]. We feel that this requirement accounted for the increased frequency of pneumonia in the GA group. The principal disadvantage of CSE is that it is timeconsuming to perform two blocks in small infants, and challenging to thread the catheters to the target spinal segment; in some cases during our study, the whole process lasted about 40 minutes. Other CSE disadvantages include the potential risk of airway compromise in a sedated child with an uncontrolled airway who is undergoing intestinal surgery. Precautions should focus on maintained patency of the infants’ airways during surgery. The limitation of this study was the fact that the epidural bolus and the distribution of the local anesthetic in the cerebrospinal fluid space may have caused a high spinal block [26]. However, we found no data about this issue in the pediatric regional anesthesia literature. In this study, injection of the epidural dose of bupivacaine occurred almost 40 minutes after the intrathecal injection (when most of the bupivacaine should have been metabolized). Another limitation of this study was that young infants have a lower concentration of albumin and alpha 1-acid glycoprotein, and the serum concentration was 50% lower in the premature neonates than the full-term neonates [27]. This fact may reduce protein binding of local anesthetics and result in a dramatic increase of the concentration of free bupivacaine, potentially predisposing infants to central nervous system toxicity. For this reason, the maximum bupivacaine infusion rate was limited to 0.2 - 0.25 mg/kg/hr for neonates and 0.5 mg/kg/hr for older infants, as suggested in previous studies [28-30]. This study showed that CSE in small infants enabled early recovery of intestinal function, diminished the need for intraoperative and postoperative opioid analgesia, and reduced the frequency of postoperative episodes of abdominal distension and pneumonia. In conclusion, CSE led to faster restoration of GI function and reduction of adverse events than GA in young infants who required elective intestinal surgery.
Acknowledgment The authors thank Dr. Arieh Bomzon for assistance in the preparation of this manuscript. Specific acknowledgment and thanks to Ilana Merhav, head librarian, Bnai Zion Medical Center.
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