General Anesthesia Combined With Quadratus Lumborum Block Reduces Emergence Delirium in Children After Laparoscopic Surgery

Abstract

Background:

Emergency delirium (ED) is a common and serious postoperative complication, especially after pediatric surgery. Quadratus lumborum block (QLB) is a critical component of the multimodal, opioid-sparing analgesia regimens, which provide effective analgesia, reduce opioid consumption, and attenuate surgical stress response. Therefore, this trial was designed to validate the hypothesis that the adjunctive use of QLB reduces the incidence of ED after laparoscopic surgery in children.

Materials and Methods:

Children aged 1 to 6 years who underwent laparoscopic surgery under general anesthesia were randomly divided into general anesthesia combined with QLB group (Group G+Q) or general anesthesia group (Group G). The primary outcome was the incidence of ED in the postanesthesia care unit (PACU), the incidence of delirium 24 hours postoperatively, extubation time, length of stay in PACU, opioid consumption, and pain score were recorded. From July 2020 to October 2022, 292 children were randomized and 287 completed the study.

Results:

The incidence of delirium in Group G+Q was significantly lower than that in Group G in PACU (16.1% vs. 47.9%, P<0.001) and 24 hours postoperatively (3.4% vs. 11.1%; P<0.05). The time of extubation time (21.2±11.4 vs. 18.2±11.8 min; P<0.05) and PACU stay in Group G were significantly longer than Group G+Q (57.2±20.3 vs. 48.9±20.4 min, P<0.01) compared with Group G.

Discussion:

General anesthesia combined with QLB can significantly reduce the incidence of ED, shorten the extubation time and PACU residence time, and improve the quality of resuscitation.

Emergence delirium (ED) is an acute brain dysfunction and psychiatric disorder that often occurs in preschool children during recovery from general anesthesia. Common symptoms of ED are nonpurposeful, resistant movements such as kicking, pulling, and waving, as well as unresponsiveness, inconsolability, and unawareness of the surrounding environment.¹ Although these symptoms are often short-lived, they increase the risk of self-injury and delayed recovery, require additional nursing staff, and consequently increase medical care costs, as well as an increased risk of developing maladaptive behaviors.² The incidence of ED has been reported to range from 10% to 80%.³ There are some predisposing factors to ED, such as preoperative anxiety, anesthesia medication, age, surgery type, and pain.^4–8 Therefore, identifying postoperative delirium-related factors and reducing the incidence of postoperative delirium has always been the research direction of anesthesiologists.

It is widely acknowledged that perioperative pain is an important contributing factor to the development of ED. While opioids remain the most effective analgesic for acute pain, their use is associated with a range of potential adverse effects, including sedation, hallucinations, and in some cases, the exacerbation or mimicry of delirium symptoms. Furthermore, severe pain and the administration of high-dose opioids perioperatively represent additional risk factors for the onset of postoperative delirium.⁹ Therefore, currently best practice guidelines for avoiding ED advocate multimodal analgesia and avoidance of opioids. Increasingly, studies have also demonstrated the potential advantages of peripheral nerve block techniques as an essential component of multimodal, opioid-sparing analgesia for improving postoperative analgesia and reducing adverse effects related to opioids in pediatric patients.^10,11 This suggests that the use of perioperative complex regional nerve blocks can have a positive effect on reducing the incidence of postoperative delirium in children.

Quadratus lumborum block (QLB) is a type of peripheral nerve block technique, a variation of the transversus abdominis plane (TAP) block, first reported by Blanco.^1,12 The QLB also referred to as an interfascial plane block by injecting a local anesthetic into the thoracolumbar fascia (TLF), a posterior extension of the abdominal wall muscle fascia extending from the lumbar spine to the thoracic spine in a craniocaudal direction. Thus, QLB produces a broad distribution of local anesthetic resulting in a large area of sensory inhibition of T7 to L1 and often used as an important component of multimodal analgesia in both adult and pediatric abdominal surgeries.^13–16 However, there are relatively few reports of the effects of QLB on postoperative delirium in children. Therefore, we hypothesized that general anesthesia combined with QLB can reduce the consumption of general anesthetics and reduce perioperative pain, which are 2 important proposed contributors to ED, and consequently reduce the incidence of ED in children. we designed this randomized controlled trial to investigate whether adjunctive use of QLB could effectively reduce the incidence of ED assessed by the Cornell Assessment of Pediatric Delirium (CAPD) score after pediatric laparoscopic surgeries under general anesthesia.¹⁷

MATERIAL AND METHODS

This single-center, randomized controlled trial was conducted from July 2020 to October 2022 in the Guangzhou Women and Children’s Medical Center. The study protocol was approved by the Ethics Committee of Guangzhou Women and Children’s Medical Center (No. 33801) and registered at the Chinese clinical trial registry (ChiCTR1900025201, http://www.chictr.org.cn). We obtained the written consent from all participants’ parents or legal guardian before the start of the study.

Patients

One- to six-year-old children who planned to undergo elective laparoscopic surgery (mainly urologic and general surgery) were enrolled in this study. Inclusion criteria: preschool children undergoing laparoscopic surgery (estimated duration of surgery more than 1 h) under general anesthesia, aged 1 to 6 years of both sexes with American Society of Anesthesia (ASA) grade I and III. All included participants were transferred to the postanesthesia care unit (PACU) for postoperative resuscitation. Exclusion criteria: (1) refusal to participate in this study, (2) preoperative mental abnormalities or neurodevelopmental disorders, (3) severe impairment of consciousness affecting delirium assessment (such as coma and deep sedation)' (4) contraindications related to regional anesthesia, and (5) congenital visual or hearing impairment.

Anesthesia, Intervention, and Perioperative Management

Participants were randomly assigned to the general anesthesia combined with quadratus lumborum block group (Group G+Q) or general anesthesia group (Group G) (allocation ratio, 1:1) based on computer-generated random numbers. Intraoperative monitoring included electrocardiogram, noninvasive blood pressure, oxygen saturation, bispectral index (BIS; Covidien IIc, MA) maintained between 40 and 60, end-tidal partial pressure of carbon dioxide (35 to 45 mm Hg), nasopharyngeal temperature (36 to 37 °C), and urine output. The intravenous induction of anesthesia with propofol (3 mg/kg; Kelun, Sichuan, China), sufentanil 0.3 mcg/kg (0.3 mcg/kg; Humanwell Healthcare, Hubei, China), cis-atracurium (0.2 mg/kg; Hengrui, Jiangsu, China) was routinely performed in all children. After endotracheal intubation, QLB was carried out by the same anesthesiologist as follows: patients were ventilated with a tidal volume of 6 to 8 mL/kg at an appropriate respiratory frequency according to their age. For patients in Group G+Q, the bilateral QLB2 was performed by the same anesthesiologist trained in ultrasound-guided regional anesthesia as previously described¹⁸: the patient is positioned supine with an ultrasound probe applied to the flank between the costal margin and the iliac crest in the anterior axillary line. When 3 abdominal muscle layers and the TLF are identified, the needle was inserted in an in-plane approach and advanced through the anterior abdominal muscles, and 0.2% ropivacaine (Jiabo, Guangdong, China) 0.5 mL/kg was injected to the posterior of the QL muscle termed the “lumbar interfascial triangle.” Anesthesia was maintained the same in both groups by inhalation of sevoflurane in 50% oxygen and intermittent intravenous administration of sufentanil and cis-atracurium. Whether the patient-controlled intravenous analgesia (PCIA) with sufentanil (0.02 mcg.kg/mL, background infusion of 2 mL/h, and a 2 mL bolus with a lockout interval of 15 min) was administered postoperatively according to the severity of injury (surgical or traumatic). After the completion of surgery, patients were transferred to the PACU and the timing for extubation was determined by the anaesthesiologists in the PACU. Investigators in the team assessed ED using the CAPD, the intensity of pain using the Face, Legs, Activity, Cry, and Consolability (FLACC) continuously after extubation until no agitation was evident, and the highest-recorded score during the PACU stay was used for evaluation. When the child develops ED in the PACU, it is remedied with 1 mg/kg propofol. Sufentanil was intravenously injected in PACU, and ibuprofen oral suspension 10 mg/kg was given in the ward if the FLACC score ≥4. The FLACC score, a validated behavioral observation pain scale for infants and children aged 2 months to 7 years, assesses pain by rating 5 behaviors (facial expression, leg position, degree of activity, quality of cry, and consolability) on a 0 to 2 scale.¹⁹

Study End-points

The primary outcome was the incidence of ED diagnosed by the CAPD score in PACU. CAPD, designed to capture all delirium subtypes, was an adaptation of the pediatric anesthesia emergence delirium (PAED).^20,21 CAPD has been proved as an effective instrument in diagnosis of delirium in pediatric surgical patients of all ages¹⁹ and scoring≥10 is considered as postoperative delirium.¹⁷ Secondary outcomes were the incidence of delirium 24 hrs after surgery, CAPD score, FLACC score, extubation time, length of stay (LOS) in the PACU (from admission to discharge of PACU), opioids and propofol consumption, the proportion of patients required remedial propofol for postoperatively delirium, adverse events, all-cause 30-day mortality, and occurrence of non-delirium postoperative complications such as vomiting, laryngospasm, hypoxia.

Sample-size Estimation

The previously reported incidence of ED after general anesthesia varies from 10% to 80%.³ In our center, the incidence of ED in children after laparoscopic surgery was about 40% and we assumed that the incidence of ED would be reduced by up to 8% in the (Group G+Q) group based on our preliminary study. With significance set at 0.05, a sample of 234 patients per group is needed to yield a study power of 0.8. Assuming a 10% loss-to-follow-up rate, we needed to enroll 292 patients.

Randomization and Blinding

The random number was generated by a biostatistician, sealed in sequentially numbered envelopes, and preserved at the study site. During the study period, patients were consecutively recruited to receive either general anesthesia combined with the QLB group (Group G+Q) or the general anesthesia group (Group G) according to the random number allocation provided by a study coordinator. Intraoperative anesthesiologists were responsible for collecting intraoperative data and did not participate in postoperative delirium assessment and follow-up. Investigators for a preoperative interview and postoperative follow-up (H.X. and W.W.) who did not participate in anesthesia and perioperative patient care had been trained before the study. Anesthesiologists and investigators did not communicate with each other regarding patients’ information during the study. Patients, investigators, and medical staff in the ward were blinded to the study group assignment.

Statistical Analysis

All data were analyzed in the intent-to-treat population. Continuous data (eg, FLACC score, CAPD score, LOS in PACU, extubation time, opioids consumption) was compared by unpaired Student t test for normal distribution data or the Mann-Whitney U test for non-normal distribution data. The difference (95% CI) between the 2 medians was calculated with the Hodges-Lehmann estimator. Categorical variables (incidence of emergency delirium and adverse events) were compared by χ² test or Fisher exact test. P-values of <0.05 were considered of statistical significance. The SPSS 14.0 for Windows (SPSS Inc., Chicago, IL) software was used for all statistical analyses.

RESULTS

From July 2020 to October 2022, 320 patients were screened for eligibility for this study, of which 292 eligible patients participated in the study and were randomly assigned into the general anesthesia group (Group G, n=146) and general anesthesia combined with QLB (Group G+Q, n=146) (Fig. 1). Three children were transferred to ICU after surgery, and 2 children were converted to open surgery. Therefore, 143 Group G+Q patients and 144 Group G patients were included in the final analysis. There were no significant significances in terms of age, weight, height, sex, and ASA grade between the 2 groups (P>0.05; Table 1).

FIGURE 1.

Flow chart of the study. ICU indicates intensive care unit.

TABLE 1.

Demographic Characteristics

	Experimental group	Control group	P
Age (mo)	38.7±17.9	37.1±18.3	0.48
Sex (M/F)	113/30	108/36	0.42
Weight (kg)	14.1±3.6	14.0±4.2	0.90
Height (cm)	97.9±12.3	95.9±14.3	0.21
ASA (I/II/III)	11/120/12	16/108/20	0.17

Data were presented as mean±SD, or number (percentage).

ASA indicates American Society of Anesthesiologists; F, female; M, male.

The incidence of ED diagnosed by CAPD in PACU was significantly lower in the Group G+Q group than in the Group G group (15.8% [23/146] with Group G+Q vs. 48.6% [71/146] with Group G; odds ratio [OR]: 0.1975, 95% CI: 0.1128-0.3437; P<0.001, Fig. 2A). Per-protocol analysis showed a similar difference in the incidence of ED between groups (16.1% [23/143] with Group G+Q vs. 49.3% [71/144] with Group G; odds ratio [OR]: 0.1971, 95% CI: 0.1121-0.3443; P<0.001).

FIGURE 2.

The primary outcome of the incidence of ED and the secondary outcomes of CAPD, FLACC. (A) Incidence of ED in the PACU; (B) incidence of ED in 24 hours after surgery in 2 groups; (C) CAPD score of children in the PACU; (D) the CAPD score of children 24 hrs after surgery; (E) FLACC score of children in the PACU; (F) FLACC score of children 24 hours after surgery; (G) extubation time in 2 groups; (H) LOS of PACU; (I) sufentanil consumption at 24 hours after surgery; “+” stands for mean, *P<0.05, **P<0.01, ***P<0.001. CAPD indicates Cornell assessment of pediatric delirium; PACU, postanesthesia care unit; ED, emergency delirium.

The incidence of ED in the ward 24 hours after surgery in the Group G+Q group was also significantly lower than that in the Group G group (3.4% vs. 11.1%; P<0.05, Fig. 2B). The CAPD score of the Group G+Q in PACU after surgery was significantly lower than that in the Group G (4.9±5.0 vs. 8.9±5.6; P<0.001, Fig. 2C), as well as the CAPD score 24 hours after surgery in the ward (1.2±2.3 with Group G+Q vs. 2.5±3.4 with Group G; P<0.01, Fig. 2D). Pain intensity assessed by FLACC were significantly reduced in Group G+Q after extubation in the PACU after surgery in the ward (1.3±1.2 with Group G+Q vs. 2.6±1.7 with Group G; P<0.001, Fig. 2E). There were no significant differences in the FLACC score 24 hours after surgery (0.29±0.81 with Group G+Q vs. 0.31±0.79 with Group G; P=0.63, Fig. 2F). In addition, consumption of the intraoperative propofol and analgesic drug remifentanil in Group G+Q were significantly lower than those of Group G (propofol, 250.8±14.7 mg vs. 287.1±14.9 mg; P<0.05; remifentanil, 169.9±16.1 vs. 216.8±21.7 mcg; P<0.05; Table 2). In the comparison of LOS in the PACU, the Group G group was significantly longer than the Group G+Q group (21.2±11.4 vs. 18.2±11.8 min; P<0.05) (Fig. 2G). Correspondently, the LOS in the PACU of Group G was significantly longer than that of Group G+Q (57.2±20.3 vs. 48.9±20.4 min, P<0.01, Fig. 2H). There were no significant differences in fluid infusion, sufentanil consumption at 24 hours after surgery (3.5±2.7 vs. 3.9±6.2 mcg; P=0.34, Fig. 2I), intraoperative BIS value, blood loss, urine output, nondelirium postoperative complications (vomiting, laryngospasm, hypoxia) between the 2 groups (Table 2). In addition, no postoperative death occurred until 30 days after surgery in both groups.

TABLE 2.

Perioperative Variables

	Evaluation index	Group G+Q (n=143)	Group G (n=144)	P
Dose of anesthetics (mean±SD)	Propofol (mg)	250.8±14.7	287.1±16.9	0.04*
	Sufentanil (mcg)	6.7±5.3	7.5±2.9	0.12
	Cis-atracurium (mg)	5.3±2.6	5.9±2.9	0.10
	Refentanil (mcg)	169.9±16.1	216.8±21.7	0.03*
	Tropasetron (mg)	1.4±0.4	1.3±0.4	0.22
	Flurbiprofen axetil (mg)	13.8±3.7	13.6±3.9	0.65
Situation of operation (mean±SD)	Infusion volume (mL)	348.0±20.9	370.1±29.1	0.39
	Bleeding amount (mL)	5.2±2.8	7.8±7.8	0.31
	Urinary volume (mL)	120.1±23.1	125.5±18.6	0.71
	Intraoperative minimum BIS	38.7±5.3	38.6±5.9	0.98
	Postoperative complications	0	0	NA

^* P<0.05

Data were presented as mean±SD, or number (percentage).

BIS indicates Bispectral Index Score; NA, not applicable.

DISCUSSION

In this prospective single-center, randomized controlled clinical trial, we aimed to explore the efficacy of general anesthesia combined with QLB to reduce the incidence of delirium after pediatric laparoscopic surgeries. Overall, we found that Group G+Q had significantly lower rates of and delirium in the PACU and 24 hours after surgery in the ward compared with Group G. Furthermore, these patients also benefited from lower pain intensity, shortened extubation time and LOS in the PACU, decreased opioids and propofol consumption. This suggests that general anesthesia combined with QLB can improve the quality of postoperative recovery and reduce the incidence of ED and related factors.

ED is still considered a mysterious complication after pediatric anesthesia. Among the identified proposed contributors, a growing number of strategies for decreasing the ED have been well studied, including nonpharmacological techniques (such as behavior management and distraction techniques) and modification of the anesthesia protocol (choice of medications, anesthetic techniques, depth of anesthesia). Postoperative pain, one of the important contributors to ED, is still difficult to distinguish from ED. FLACC scale and CAPD used in this trail have been applied to differentiate between ED and pain well in children with high inter-rater variability, reliability and validity.^17,19 Although regional anesthesia may decrease pain and opioid requirements, there is no definitive evidence to suggest that combination with general anesthesia, it decreases ED. We speculate that there are several reasons for decreased ED in Group G+Q. Firstly, multimodal analgesia is a trend in anesthesiology, and perioperative pain is an important risk factor for inducing ED.²² QLB has been shown to provide good analgesic efficacy. Xue et al²³ found that QLB significantly reduced visceral VAS scores and delayed the first time to rescue analgesia compared with general anesthesia alone during the laparoscopic sleeve gastrectomy. Priyadarshini et al²⁴ found that QLB significantly prolonged analgesia and reduced opioid consumption compared with transverse abdominis plane (TAP) and ilioinguinal/iliohypogastric (II/IH) nerve blocks in pediatric inguinal hernia repair. Some studies have found that this reduced need for analgesia can be observed up to 48 hours postoperatively.²⁵ Therefore, better analgesia may be the main mechanism by which QLB reduces the occurrence of ED. Secondly, Punjasawadwong et al²⁶ found that the depth of anesthesia is closely associated with ED by which using BIS guidance to optimize anesthesia could reduce the risk of ED. In addition, inhaled anesthetics such as sevoflurane and opioids use is another modifiable contributor to ED. Consistently, the intraoperative propofol and refentanil doses of Group G+Q were significantly lower than those in Group G (Table 2) with the comparable intraoperative BIS values in the 2 groups, suggesting that composite QLB may help reduce the incidence of ED by reducing the dose of intraoperative sedatives and analgesics. However, there was no statistically significant amount of sufentanil remediation and FLACC score in the 2 groups 24 hours after surgery (Figs. 2F, I), which is probably because the maintenance time of QLB was about 4 to 6 hours.

Moreover, current studies have shown that regional nerve blocks can reduce the release of inflammatory factors, which is a proposed mechanism underlying postoperative delirium and cognitive dysfunction. Huang et al found that sciatic nerve block can significantly reduce the concentration of inflammatory factors such as IL6, IL-8, TNF-α compared with epidural block, thereby alleviating the inflammatory response.²⁷ Coincidently, Zhu et al²¹ found that QLB can reduce postoperative inflammatory indicators such as HMGB1, TNF-α, and IL-6, thereby improving patients’ postoperative cognitive function.²¹ Stress and inflammation during surgery are also considered to be factors in the occurrence of ED, and delayed inflammatory response can even cause postoperative cognitive dysfunction,²⁸ but most of the relevant studies are in the elderly. However, our results found that QLB can decrease the incidence of ED in children and improve the postoperative recovery quality which might be due to the reduced postoperative inflammatory indicators. In conclusion, the reduced incidence of ED in children may be a combination of the above factors.

There are many studies to reduce the occurrence of ED through combined anesthesia, such as epidural-general anesthesia, but the related complications and individual risks need to be considered. Li et al²⁹ found that the incidence of delirium in older patients undergoing major chest and abdominal surgery with epidural-general anesthesia was one-third that of general anesthesia alone, but the risk of hypotension was increased by 50%. In this study, we found that the incidence of ED can be reduced to 15.8% through adjunct QLB to general anesthesia. Compared with epidural anesthesia, QLB has fewer contraindications and complications, especially under ultrasound guidance, better circulation, and respiration maintenance, which is very beneficial and safe for children.

The limitations of this study are: (1) the use of postoperative analgesia pumps in some children, may interfere with our delirium assessment results, particularly in the general anesthesia group; (2) distinguishing between negative behaviors (eg, pain) and delirium status in younger children is still challenging for nonpsychiatric specialists including anesthesiologists; (3) we only collected data within 24 hours after surgery for study and did not follow up the long-term cognitive function and sleep status after surgery which is also something we should be concerned about.

CONCLUSION

ED is a common and serious postoperative complication, especially in preschool children during the perioperative period. General anesthesia combined with QLB can significantly decrease the incidence of ED, shorten the extubation time and LOS of PACU, decrease the postoperative pain intensity, reduce the consumption of opioids and general anesthetics, and improve the quality of postoperative recovery without QLB-related complications. In conclusion, combined use of QLB might be a promising strategy for pediatric laparoscopic surgeries.