
==== Front
Pulm Circ
Pulm Circ
10.1002/(ISSN)2045-8940
PUL2
Pulmonary Circulation
2045-8932
2045-8940
John Wiley and Sons Inc. Hoboken

10.1002/pul2.12435
PUL212435
Research Letter
Research Letter
Impact of general anesthesia on the echocardiographic assessment of right ventricular function in pediatric patients with pulmonary arterial hypertension
SIMPKIN et al.
Simpkin Charles T. http://orcid.org/0009-0007-3295-8335
1 charles.simpkin@childrenscolorado.org

McElroy Billy J. 2
Morgan Gareth J. 1
Dunbar Ivy David 1
Burkett Dale A. 1
Twite Mark D. 2
Frank Benjamin S. 1
1 Department of Pediatrics, Division of Cardiology University of Colorado Denver Aurora Colorado USA
2 Department of Anesthesiology University of Colorado Denver Aurora Colorado USA
* Correspondence Charles T. Simpkin, Department of Pediatrics, Division of Cardiology, University of Colorado Denver, 13123 E. 16th Ave, Box B100, Aurora, CO 80045, USA.
Email: charles.simpkin@childrenscolorado.org

20 9 2024
7 2024
14 3 10.1002/pul2.v14.3 e1243523 8 2024
21 5 2024
27 8 2024
© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Abstract

One of the great diagnostic challenges for children with pulmonary arterial hypertension is the need for general anesthesia (GA) to enable successful right heart catheterization. Here, for the first time, we describe how echocardiographic estimates of right ventricular function and pulmonary pressures change in pediatric patients during GA.

anesthesia
eccentricity index
hemodynamics
pulmonary arterial hypertension
right ventricular function
National Institute of Health 10.13039/100015326 NIH T32 HL7171‐45 NIH/NCATS Colorado CTSAUM1TR004399 Jayden DeLuca Foundation source-schema-version-number2.0
cover-dateJuly 2024
details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.4.8 mode:remove_FC converted:20.09.2024
Simpkin CT , McElroy BJ , Morgan GJ , Dunbar Ivy D , Burkett DA , Twite MD , Frank BS . Impact of general anesthesia on the echocardiographic assessment of right ventricular function in pediatric patients with pulmonary arterial hypertension. Pulm Circ. 2024;14 :e12435. 10.1002/pul2.12435
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pmcINTRODUCTION

The gold standard for the diagnosis of pulmonary arterial hypertension (PAH) in both adults and children remains direct hemodynamic assessment during right heart catheterization (RHC). 1 However, one of the major differences between these two groups is that children typically require general anesthesia (GA) to tolerate RHC. 2 The need for GA introduces an unpredictable variable when it comes to interpreting results of RHC in children.

Under GA, there are a host of factors that have competing physiologic effects on the pulmonary vascular circulation that may alter the results of RHC. These include the effects of positive pressure ventilation (PPV) on ventricular preload and systolic function, 3 blood pH and hypercarbia on pulmonary vascular tone, 4 and the impacts of anesthetic drugs on myocardial function and systemic/pulmonary vascular resistances. 5 , 6 , 7 , 8 Despite this, we must acknowledge the necessity of anesthesia in ensuring the comfort and safety of pediatric patients during RHC. It is therefore important that the clinician interprets hemodynamic data in context and understands there may be limitations when data obtained during RHC under GA is extrapolated to the patient's free‐breathing, awake state.

Echocardiography remains the primary modality by which patients are screened and followed for PAH. Few‐if‐any prior studies have assessed how echocardiographic‐derived metrics obtained in an awake patient change when those same patients are under GA. The aims of this retrospective study are to evaluate how commonly used echocardiographic estimates of PAH change under GA, and how these measures relate to invasively obtained hemodynamics.

METHODS

Twelve children aged 1−16 years (median 8.0 year) with Group 1 (idiopathic, n = 9) or Group 3 (pulmonary etiology, n = 3) PAH underwent a clinically indicated RHC under GA. During the study period 2016−2021, echocardiograms were obtained while under GA and during a preceding clinic visit (within 2 weeks of RHC with no interceding clinical changes between studies). Tricuspid annular plane systolic excursion (TAPSE), right ventricular end diastolic area (RVEDA), right ventricular fractional area change (RV FAC), systolic eccentricity index (EIs), and the maximum velocity from the tricuspid regurgitation (TR Vmax), RV free wall longitudinal strain (RVFWLS), and the RV:LV end‐systolic ratio were measured in each condition. TR Vmax was only measured from complete Doppler envelopes, and were then utilized to estimate right ventricular systolic pressure (RVSP) using the modified Bernoulli equation. These were compared to invasively measured mean pulmonary artery pressure and systolic pulmonary artery pressure (PASP), indexed pulmonary vascular resistance, and the RV systolic pressure (RVSP). Wilcoxon Signed‐Rank test and Spearman's rho were performed to analyze data using SPSS Statistics (IBM Corp., version 23 Armonk, NY, USA). Patients who had missing data from either condition due to inadequate imaging quality were excluded from paired analyses. The study was approved by the local Institutional Review Board and written informed consent was obtained from the patient or legal guardian.

RESULTS

All 12 patients received a combination of anesthetic agents during their RHC: 11/12 were induced with an inhaled volatile anesthetic agent (sevoflurane) and maintained at under one minimum alveolar concentration of volatile anesthetic agent, 11/12 received adjunct propofol infusion during the case (median dose 50 mcg/kg/min), 12/12 received fentanyl (median dose 2.4 mcg/kg), 3/13 received bolus doses of ketamine and one patient received etomidate. All patients received crystalloid fluids (median 10 mL/kg). Nine patients received PPV with an endotracheal tube, while three had spontaneous ventilation with a laryngeal mask airway. The measured end‐tidal CO2 (ETCO2) ranged from 31 to 38 mmHg (median 33.5 mmHg).

Comparison of median values for outcome variables between conditions are in Table 1. The systemic systolic blood pressure was significantly lower during anesthesia, while heart rate was unchanged. RV:LV ratio, TAPSE, RVEDA, RV FAC, EIs, RVFWLS, and RVSP:SBP ratio did not change significantly between conditions. TR Vmax was significantly lower in the anesthesia condition (3.23 [2.8–3.9] m/s vs. 4.0 (3.2–4.8) m/s, p < 0.05).

Table 1 Median (IQR) values for physiologic and echo parameters between conditions.

	Awake median (IQR)	General anesthesia median (IQR)	Median difference (IQR)	p Value	
Systolic BP (mmHg)	110.0 (94.2–114.7)	77.5 (71.0–88.8)	32.5 (23.3–25.9)	0.003a	
Diastolic BP (mmHg)	63.5 (53.5–66.8)	43.0 (41.0–46.5)	20.5 (12.5–20.3)	0.005a	
Heart Rate (bpm)	77.5 (72.5–84.8)	69.0 (62.3–78.8)	8.5 (10.2–6.0)	0.99	
RVEDA (cm2)	18.1 (14.7–22.5)	13.5 (11.5–21.5)	4.6 (3.2–1.0)	0.18	
RV:LV ratio	1.20 (1.01–1.45)	1.19 (1.10–1.36)	0.06 (−0.60 to 0.09)	0.42	
TAPSE (cm)	1.9 (1.5–2.2)	1.8 (1.4–2.1)	0.1 (0.1–0.1)	0.75	
RV FAC (%)	29.2 (22.5–33.9)	22.9 (18.5–30.1)	6.3 (4.0–3.8)	0.13	
RVFWLS (%)	−23.2 (−30.2 to −19.5)	−17.6 (−24.0 to −14.5)	−5.6 (−6.2 to −5.0)	0.80	
TR Vmax (m/s)	4.0 (3.2−4.8)	3.23 (2.8−3.9)	0.77 (0.4−0.9)	0.03a	
Eccentricity Index	1.4 (1.3–1.6)	1.4 (1.3–1.8)	0.0 (0.0–0.2)	0.16	
RVSP:SBP ratio	0.57 (0.43−0.86)	0.50 (0.43−0.76)	−0.01 (−0.16 to 0.18)	0.94	
Sub‐Group Analysis	
RV FAC (%)

Group 1 (n = 5)

	33.9 (31.9–37.2)	21.8 (16.9–25.8)	12.1 (15.0–11.4)		
RV FAC (%)

Group 2 (n = 6)

	21.7 (13.4–27.7)	26.5 (15.0–35.2)	−4.8 (−1.6 to −7.3)		
Note: Group 1 had RV FAC > 30% in the awake condition, group 2 had RV FAC < 30% in the awake condition.

Abbreviations: RVEDA, right ventricular end diastolic area; RV FAC, right ventricular fractional area change; RVFWLS, right ventricular free wall longitudinal strain; RV:LV ratio, right ventricular to left ventricular end‐systolic ratio, RVSP, echo‐estimated right ventricular systolic pressure (estimated from the TR Vmax); SBP, systolic blood pressure; TAPSE, tricuspid annular systolic plane excursion; TR Vmax, maximum velocity from the tricuspid regurgitation.

a Denotes statistical significance;

bDenotes statistical significance in comparison of degree of median change between group 1 and group 2 using Wilcoxon Signed‐Rank test.

John Wiley & Sons, Ltd.

A sub‐group analysis was performed comparing patients with RV FAC ≥ 30% and those with RV FAC < 30% on their awake echocardiogram. Patients in the >30% FAC group were noted to have a significantly greater decline in their RV FAC from the awake to the GA state (12.1% [15.0–11.4] vs. −4.8% [−1.6 to −7.3], p < 0.05). The degree of change in TAPSE was not significantly different between the preserved and decreased RV FAC groups (p = 0.55). Similar analysis of RVFWLS was not performed given 7 of 12 patients had missing data.

The TR Vmax in the GA condition correlated well with invasively measured PASP (ρ = 0.92, p < 0.001), whereas the awake TR Vmax did not (ρ = 0.50, p = 0.11). EIs in both conditions were strongly correlated to invasive hemodynamics (vs. PASP, Awake: ρ = 0.91 p < 0.001 and GA: ρ = 0.90, p < 0.001).

There were no significant correlations between the degree of change in echocardiographic metrics and the amount of anesthetic that the patient received (p > 0.05). Echocardiographic metrics were not correlated with the ET‐CO2, FiO2, or tidal‐volume while measurements were being performed (p > 0.05). There were no identifiable differences in the amount or type of anesthesia used in patients with normal, compared to those with abnormal RV function.

DISCUSSION

To our knowledge, this is the first study to evaluate how commonly used echocardiographic measures of RV function and surrogates of pulmonary artery pressures change in children with PAH under GA. In two of the three echocardiographic surrogates of RV function (RV FAC, and RVFWLS), there was statistically nonsignificant trend towards worsening function under GA. TAPSE was unchanged between the two conditions. TR Vmax was noted to be significantly lower during GA, which was likely due to the proportional decrease in systolic blood pressure under GA as indicated by stable RVSP:SBP and EIs between conditions.

The subset of patients with RV FAC > 30% in the awake condition had a significant worsening of their RV function, whereas those with an RV FAC < 30% in the awake state did not have a significant change in their function under GA. This is similar to a study on adult patients that found the same pattern utilizing RV ejection fraction from 3D echo. 9 We could not identify any significant difference in the amount or type of anesthetic agents given between the two groups, although three of the patients who were allowed to spontaneously breathe with an LMA were in the abnormal‐function group. As this pattern has been shown in two different studies suggests there is some variability in myocardial reserve between patients that we are unable to quantify with our current imaging metrics. This is an important area for future research.

TR Vmax was significantly lower in the GA condition, implying lower RVSP in this state. The reason for this apparent drop in RV pressures is likely multifactorial. It stands to reason that an awake child could have higher RV pressures compared to when they are fully sedated. The anesthetic agents used in these patients likely cause concurrent decreases in SVR and PVR, keeping the overall ratio similar between the awake and GA states. This idea is supported by the absence of significant change that we observed in the ratio between RVSP:SBP. Furthermore, to avoid hypercarbia‐induced pulmonary vasoconstriction, ETCO2 was kept lower during mechanical ventilation under GA compared to an awake spontaneously breathing state. This may further decrease measured pulmonary artery pressures during RHC under GA. Under GA the total oxygen consumption is also likely lower than in the awake state, so cardiac output may fall as an adaptive response to decreased metabolic demand. In this lower cardiac output state, the estimated RVSP as measured by the TR Vmax would also be lower.

We also noted the TR‐Vmax when awake did not correlate well with the invasively measured hemodynamics. While all the values for TR Vmax for these patients would be well above what is considered normal, this finding suggests that some caution should be applied when using TR Vmax to predict the exact hemodynamic values a patient may have while under anesthesia.

EIs has gained favor for its simplicity and ability to quantify the degree of interventricular septal flattening. Here, EIs was not noted to change between conditions and there was a strong correlation with invasively measured hemodynamics. 10 This is likely reflective of EIs' ability to estimate the ratio of RV‐to‐LV pressures. As the RVSP falls with induction of anesthesia, so does the systemic blood pressure. This concept was further supported by the lack of significant change in RVSP:SBP ratio between conditions. These findings further reinforce EIs as a reliable tool in estimating invasive hemodynamics and the complex ventricular‐ventricular interactions in patients with PAH.

Our findings in this study are limited by its retrospective design and small sample size. The variability in amounts and types of anesthetic agents used, as well as the types of airway and modes of ventilation that were employed also limit its generalizability.

This study reflects the heterogenous nature of pediatric PAH and how anesthesia is delivered to these patients. Our findings support the idea that invasive hemodynamics taken under GA may not be reflective of a patient's awake, free‐breathing state. In particular, the estimated PA systolic pressure seems to fall proportionally to the SVR. There also seems to be a subset of patients who have a more pronounced decrement in their right ventricular function under GA. Larger, prospective trials using standardized protocols of anesthetic and ventilator management are needed to better understand exactly how GA may impact hemodynamics in pediatric patients with PAH.

AUTHOR CONTRIBUTIONS

Charles T. Simpkin conceived the project, analyzed data, and wrote the manuscript. Billy McElroy and Mark Twite assisted with data collection and manuscript review. David Dunbar Ivy, Dale A. Burkett, and Gareth J. Morgan helped with manuscript review. Benjamin S. Frank supervised the project.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

ETHICS STATEMENT

The study was approved by the local Institutional Review Board and written informed consent was obtained from the patient or legal guardian.

ACKNOWLEDGMENTS

CTS funded by NIH grant T32 HL7171 as well as the Jayden de Luca Foundation. This study funded by NIH/NCATS Colorado CTSA grant UM1TR004399.
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