Impact of high spinal anesthesia in pediatric congenital heart surgery on postoperative recovery: a retrospective propensity score-matched study

Introduction

Cardiac surgery is well known to result in a significant stress and inflammatory response which may subsequently impact clinical outcomes (1,2). Historically, high-dose systemic opioids were used to mitigate this stress response; however, this approach often prolonged the postoperative recovery period. To attenuate the stress response while minimizing opioid dosage, neuraxial block techniques, including spinal, caudal, or epidural anesthesia, have been employed in cardiac surgeries (3-15). In this context, high spinal anesthesia (HSA), a method involving a deliberate high spinal block using a high dose of intrathecal local anesthetic, has been applied in cardiac surgery (5,7,9,10,16,17). However, research on HSA in the pediatric population is largely limited. Previous studies have primarily investigated it in a descriptive manner with a small cohort (3,14) and few studies have compared the impact of HSA with non-HSA techniques on postoperative recovery.

Therefore, the primary aim of this study is to evaluate the impact of HSA on fast-track extubation and recovery following pediatric congenital heart surgery. We hypothesized that HSA combined with general anesthesia (GA) facilitates fast-track postoperative recovery, including shorter extubation time, length of stay (LOS) in the intensive care unit (ICU) and the hospital following pediatric congenital heart surgery, as compared to anesthetic care with GA alone. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1157/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). A single center, propensity score-matched retrospective cohort study was conducted at the University of Iowa Hospital and received approval from the Ethics Committee (University of Iowa Institutional Review Board; #201911151). Individual consent for this retrospective analysis was waived. Patients aged less than 18 years who underwent elective congenital heart surgeries, classified as Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) (18) score 3 or less, at the University of Iowa Hospital from November 1, 2010 through December 31, 2020 were included. Cases with a RACHS-1 score of 4 or above were excluded, as patients undergoing such procedures are not typical candidates for fast-track extubation. Emergency surgical cases were also excluded from the study. Data were retrieved from the electronic medical records (Epic Systems, Verona, WI, USA) and the Society of Thoracic Surgeons database on outcome measures. The cases were divided into two groups: those with HSA in combination with GA (HSA group) and those with GA alone without any additional neuraxial blocks (GA group) based on the intraoperative anesthetic record details.

In both groups, inhalational induction was typically chosen. For any patients with a preexisting intravenous (IV) line, IV induction was typically chosen. The detailed procedure in a case for inhalational induction was as follows: After standard American Society of Anesthesiologists monitors were applied, GA was induced with sevoflurane and a peripheral IV was placed. The patient was endotracheally intubated with rocuronium. In the HSA group, after a radial arterial line and a central venous line were established under GA, the patient was placed in the lateral decubitus position, and intrathecal medications were injected at a lumbar level between L2 and L5 (between L3 and S1 for neonates and infants) via a 27-gauge spinal needle. The intrathecal medications consisted of 0.75% hyperbaric bupivacaine (0.2 mL/kg for the first 10 kg weight, then an additional 0.1 mL/kg after the first 10 kg, limited up to 8 mL), with preservative-free morphine (7 mcg/kg, limited up to 500 mcg). Immediately after the intrathecal injection, the patient was placed in the supine position at 30 to 45 degrees Trendelenburg to facilitate the cephalad spread of spinal anesthesia. Mydriasis confirmed the total spinal block. GA was maintained with sevoflurane or isoflurane [0.5–1.0 minimal alveolar concentration (MAC)]. Intravenous heparin for cardiopulmonary bypass was administered at least one hour after the intrathecal injection. For the patients in the GA group, GA was induced in a similar manner, but no neuraxial block was provided. GA was maintained with sevoflurane or isoflurane (0.5–1.0 MAC) with low-to-moderate doses of intravenous opioids (equivalent to 10–30 mcg/kg of fentanyl) intraoperatively. Opioids used were fentanyl, remifentanil, hydromorphone and/or morphine. An excessive dosage of opioids was avoided to facilitate fast-track recovery. In both the HSA and GA groups, the patients were extubated in the operating room at the discretion of the attending pediatric cardiac anesthesiologist of the respective cases. If not extubated in the operating room, the patient was extubated in the ICU when meeting the extubation criteria per our institutional protocol.

The comparison was made between the two groups (HSA group vs. GA group). The primary outcome was the odds of patients being extubated in the operating room. Secondary outcomes included extubation within 6 hours after ICU admission, LOS in the ICU, and LOS in the hospital. Time to extubation was also recorded and compared between groups. Additionally, postoperative opioid requirements, and pain scores as measured by the Face, Legs, Activity, Cry, Consolability (FLACC) scale were compared between the groups during the first 24-hour and the second 24-hour postoperative periods. Opioid doses were converted into milligram morphine equivalents (MME). Any complications, such as epidural hematoma or HSA-induced hemodynamic collapse, were also reviewed.

Statistical analysis

All data were tabulated and presented as counts n (%), means [± standard deviation (SD)], or medians [interquartile range (IQR)]. All the statistical analysis was performed using SPSS 26 (IBM SPSS Statistics for Windows, Version 20.0; IBM Corp, Armonk, NY, USA). In order to control for patient characteristics, patients in the HSA and GA groups were matched at a 1:1 ratio using propensity score matching. Propensity scores were determined using an error allowance between matches set to 0.15. Covariates for matching included age, gender, weight, RACHS-1 score, surgical time, use of cardiopulmonary bypass, and bypass time to construct the model. Baseline demographics and covariates were compared before and after propensity score matching. Prior to matching, balance of covariates was assessed and there was significant imbalance of covariates, determined by standardized mean difference greater than 10% between groups. Normality of outcome variables was determined by applying the Shapiro-Wilk test. The groups were compared using the Mann-Whitney U-test for continuous variables, and dichotomous variables were analyzed using the chi-square test. We did not correct for multiple comparisons in this analysis. Odds ratios (OR) were calculated along with 95% confidence interval (CI) for outcome variables such as extubation in the operating room and extubation within 6 hours. A P value less than 0.05 was considered statistically significant. In order to estimate extubation between groups, a Kaplan-Meier curve was generated. The outcome variable for this curve was percentage of patients remaining intubated. Patients who were not extubated during the observed period were considered censored observations. Statistical significance between groups was determined using two-sided log-rank tests.

To ascertain the effects of various factors on the primary outcome of extubation in the operating room, a multivariate logistic regression was performed. Factors included in the model were use of HSA, age, gender, RACHS-1 classification, primary vs. repeat surgery, ASA status, weight, height, anesthesia time, surgery time, cardiopulmonary bypass time, primary surgeon, and primary anesthesiologist. The goodness of fit of the logistic regression model was determined using the Hosmer-Lemeshow test.

Results

Between November 1, 2010, and December 31, 2020, a total of 1,188 pediatric cardiac surgeries were performed. Of these, 566 cases were eligible for this study (Figure 1). There were 224 cases in the HSA group and 342 cases in the GA group. After propensity-score matching, 197 from each group were used for analysis. Baseline patient characteristics, RACHS-1 scores, bypass time, and surgical time were not significantly different between the two groups (Table 1). Thirty-five patients in the HSA group remained unmatched due to the lack of comparable cases and patient characteristics in the GA group. Types of surgery are shown in Table 2.

Figure 1 Flowchart of the study. *, cases with Risk Adjustment for Congenital Heart Surgery—1 score of 4 or above were excluded.

Table 3 shows the outcomes for fast-track extubation and LOS in the ICU and the hospital. The rate of extubation in the operating room was significantly higher in the HSA group (65.5% vs. 33.5%, OR 3.82, 95% CI: 2.5 to 5.8, P<0.001). The rate of extubation within 6 hours after ICU admission was also significantly higher in the HSA group (82.7% vs. 61.9%, OR 2.95, 95% CI: 1.9 to 4.7, P<0.001). LOS in the ICU was significantly shorter in the HSA group compared to the GA group [median 5.1 (IQR 2.6–7.7) vs. 8.0 (0.8–15.2) days, P<0.001]. The LOS of the hospital was not significantly different between the HSA and GA group [median 8.7 (3.7–13.8) vs. 9.5 (5.9–13.1) days, P=0.60, respectively]. Figure 2 depicts time to extubation over a one-week postoperative period.

Figure 2 Percentage of patients requiring intubation over one week postoperatively. GA, general anesthesia; HSA, high spinal anesthesia.

The multivariate logistic regression model explained 25% of the variance for the likelihood of getting extubated in the operating room and correctly classified 70% of cases. The odds of getting extubated in the operating room with the use of HSA was 3.63 times higher than in the GA group. Increasing surgical duration significantly influenced the model (OR =0.98; P<0.001), although the effect was less pronounced than that of HSA. None of the other covariates had statistically significant effects on the dependent variable of extubation in the operating room (χ²=5.586, P=0.69).

Table 4 shows the postoperative opioid requirement and pain scores. The postoperative opioid requirement in the first 24 hours was significantly lower in the HSA group. The opioid requirement in the second 24 hours was not significantly different between groups. The maximal and average FLACC pain scores were significantly greater in the HSA group in the first 24 hours. In the second 24 hours, maximal and average pain scores were not significantly different between groups. In-house mortality (0% in both groups) and 30-day mortality (1.0% in the HSA group and 2.0% in the GA group, P=0.68) were not significantly different between groups. Complications related to HSA, such as intractable hypotension and epidural hematoma, were not observed in the HSA group.

Discussion

The current retrospective study aimed to investigate the impact of HSA on postoperative recovery in pediatric congenital heart surgery. The results showed that the pediatric patients in the HSA group had higher odds of getting extubated in the operating room and spending less time on postoperative mechanical ventilation and in the ICU. Furthermore, HSA was performed without any complications, such as epidural hematoma or clinically significant hemodynamic sequelae.

Fast-track extubation is gaining great interest in pediatric congenital heart surgery (19-21). The potential benefits of early extubation may include a lower incidence of ventilator-associated pneumonia and laryngotracheal trauma, less postoperative inotropic support, shorter ICU, and hospital stay, and reduced cost (22-24). Furthermore, in certain patients, such as patients with single-ventricle physiology who undergo cavopulmonary connection, early extubation with minimal opioid use is particularly beneficial because it improves the hemodynamics by increasing venous return and restoring vigorous spontaneous ventilation (25-27). Therefore, along with other emerging locoregional techniques (28), HSA could be a useful method in pediatric congenital heart surgery. Yet, although promising results have been published in the adult cardiac surgery population (5,9,10), few studies have been conducted in the pediatric population.

One reason that may have prevented broader use of HSA in the pediatric population is the lack of literature (29) to investigate the benefits that the current study has been addressing. HSA induced by the high dose of intrathecal bupivacaine provides a complete sensory block against surgical stimulus, allowing for no or fewer intraoperative IV opioid requirements. This is particularly beneficial at the beginning of surgery when the patient receives the most intense surgical stimulation with sternotomy and pericardiotomy. The sensory block from the high-dose bupivacaine eventually subsides after several hours by the completion of surgery; however, the intrathecal morphine provides adequate analgesia during the first 24 hours of the postoperative period (30,31). This was evident by the decreased opioid requirement during the first 24-hour postoperative period in the HSA group in the current study. Subsequently, combining the HSA technique with GA could minimize the risk of opioid-induced respiratory suppression by reducing the perioperative opioid requirement while maintaining adequate pain control, leading to faster extubation and postoperative recovery.

The high-dose intrathecal morphine administered in the current study is based on a dosing regimen derived from historical data and existing literature. Over two decades ago, studies suggested that recommended dosages for pediatric cardiac surgery ranged from 5 to 10 mcg/kg (3,14); our institution adopted 7 mcg/kg as the standard dose. Although the use of high-dose intrathecal morphine plays a crucial role in HSA for effective postoperative pain management, it is important to be aware of its potential side effects. Common side effects include postoperative nausea and vomiting, pruritus, and urinary retention, along with more serious risks such as respiratory depression (32). The incidence of these side effects, particularly respiratory depression (33), may increase with a higher dosage, underscoring the need for careful application and vigilant monitoring. All cardiac surgery patients undergo close postoperative monitoring in the ICU, facilitating the safe administration of high-dose intrathecal morphine, as potential side effects can be promptly managed. This approach enhances patient safety by combining effective analgesia with vigilant patient care. However, further research is still necessary to refine dosing strategies and mitigate risks associated with the use of intrathecal morphine in pediatric cardiac surgery, aiming to find an optimal balance between efficacy and safety.

As discussed previously, the intrathecal morphine provides better pain control during the first 24 hours postoperatively in cardiac surgery (30,31). However, while the opioid requirement was significantly lower in the HSA group, the pain score in this group was significantly higher in the first postoperative 24 hours compared to that in the GA group (Table 4). This is likely attributed to the fact that the patients in the GA group spent more time on postoperative mechanical ventilation and were sedated, leading to a lower pain score in the first postoperative 24 hours.

In terms of neuraxial anesthesia, there are concerns about the development of epidural hematoma in the context of full-dose heparinization during cardiac surgery. However, the risk of such hematoma formation is considered remote, with an estimated incidence of approximately 1 in 3,500 with epidural anesthesia (29), and this risk may be even lower with spinal anesthesia. As a result, our single-center cohort study, with a sample size of 224, is not sufficient to fully assess the safety of HSA regarding epidural hematoma formation. Additionally, concerns exist about potential catastrophic hemodynamic instability caused by HSA-induced sympathectomy, particularly in patients with significant underlying cardiac disease. Nevertheless, HSA may not cause catastrophic effects on hemodynamics and could be clinically manageable without difficulty in the pediatric cardiac surgery population, as represented by our study cohort with a mean age of 4.1±4.5 years, due to the relatively underdeveloped sympathetic nervous system in this age group (34,35). Although we did not observe any significant complications, such as epidural hematoma or catastrophic hemodynamic disturbances, our study was not specifically designed to evaluate the safety of HSA in pediatric cardiac surgery. Larger cohort studies will likely be necessary to further explore the safety of HSA in this population. Therefore, the safety of HSA, along with its associated risks and benefits, should be carefully considered on a case-by-case basis.

The current study has several limitations. Due to the retrospective nature of the study design, results were likely subjected to confounding and selection bias. Despite appropriate adjustments such as propensity matching for baseline known confounders, including age, gender, weight, RACHS-1 score, surgeon, anesthesiologist, surgical time, use of cardiopulmonary bypass, and bypass time, the possibility of unmeasured or residual confounding factors between the groups cannot be ruled out. Further, the decision to perform HSA was dependent on the comfort and skill of the assigned cardiac anesthesiologists. During the study period, four out of eight pediatric cardiac anesthesiologists had never performed HSA, affecting the allocation of patients to the HSA or GA groups. This discrepancy reflects the pragmatic nature of the study, mirroring the real-world scenario, where some anesthesiologists believe in HSA and are more comfortable in offering HSA in cardiac surgical patients while others are not. While this was factored into our statistical analyses and reflects the current state of HSA for cardiac surgery, in which the technique is highly dependent on the anesthesiologist, we cannot completely rule out the influence of other aspects of anesthesia care provided by each anesthesiologist on the study results. Additionally, performance bias, arising from knowledge of the type of anesthesia—whether HSA was conducted or not—likely influenced management and, consequently, could have affected the outcomes of the study. Moreover, over the duration of the study, changes in institutional practices and the skills of anesthesia and surgical practitioners could have significantly influenced outcomes. Lastly, the current study excluded emergency surgeries and congenital heart surgeries with a RACHS-1 score of 4 or above; thus, the outcomes may differ for patients undergoing these procedures. Considering the study’s limitations, definitive evidence is still needed. Future prospective trials could more accurately assess the efficacy of HSA in pediatric cardiac surgery. Nevertheless, the results of the current study remain relevant due to the high magnitude of effects observed (36), supporting the notion that HSA may facilitate early extubation and recovery. Therefore, our findings provide valuable insights into the application and efficacy of HSA in pediatric cardiac surgery, contributing to the existing body of knowledge in a field where evidence is scarce.

Conclusions

The current propensity score-matched cohort study demonstrated that combining HSA with GA was significantly associated with increased odds of extubation in the operating room compared with GA alone in pediatric cardiac congenital heart surgeries of RACHS-1 score 3 or less. HSA was also associated with reduced time on postoperative mechanical ventilation, shorter stays in the ICU, and a lower opioid requirement in the first 24 hours postoperatively. These results need to be validated by future prospective randomized trials.

Acknowledgments

The authors thank Kenichi Ueda, MD, PhD, for critical discussion of the manuscript. The preliminary results of the study were presented at the 22nd Annual Pain Medicine Meeting of the American Society of Regional Anesthesia and Pain Medicine (ASRA) on November 10, 2023, and received a Best of Meeting Award.

Funding: This study was funded by the 2020 University of Iowa Clinical and Educational Pilot Grant Program.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1157/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1157/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1157/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1157/coif). R.S. is a consultant for CIVCO Medical Solutions (https://www.civco.com/). S.H. reports that this study was funded by the 2020 University of Iowa Clinical and Educational Pilot Grant Program. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the University of Iowa Institutional Review Board (#201911151) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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