No difference among groups was observed in mean left-sided rScO2 values before aortic cross-clamping (72% ± 10%, 77% ± 13%, and 77% ± 11% for sevoflurane, SNP, and NTG, respectively, P = 0.57). Three possible responses to aortic cross-clamping were observed in left rScO2 measurements: a decrease of left rScO2 in 2 patients of each group (maximal relative decrease of −5% and −17% for sevoflurane, −5% and −47% for SNP, −28% and −33% for NTG, P = 0.58 between groups), no change in left rScO2 in 1 patient in the sevoflurane group, 2 patients in the SNP group, and in 2 patients in the NTG group, whereas an increase in left rScO2 was observed in the remaining patients (sevoflurane, n = 7, 10% ± 7%; SNP, n = 6, 13% ± 4%; NTG, n = 6, 17% ± 19%, P = 0.32 between groups). No differences among groups were observed in the maximal relative changes in left rScO2 values in response to aortic cross-clamping (SNP versus sevoflurane: mean difference −0.7%, 99% CI −31% to 29%, P = 1.0; SNP versus NTG: mean difference −1.8%, 99% CI −32% to 28%, P = 1.0; sevoflurane versus NTG: mean difference −1.1%, 99% CI −31% to 29%, P = 1.0).
The following additional observations were made regarding changes in right rScO2, SrO2, and SmO2. No differences among groups were observed in mean right rScO2 values before aortic cross-clamping (P = 0.69) and in maximal relative change in right rScO2 values in response to aortic cross-clamping (P = 0.4) (Table 3). SrO2 and SmO2 showed a rapid and significant decrease after aortic cross-clamping in all groups, reaching a plateau phase for SrO2 within 8.6 minutes, 7.4 minutes, and 10.0 minutes for sevoflurane, SNP, and NTG, respectively (P = 0.08 among groups) and within 9.4 minutes, 6.8 minutes, and 9.9 minutes for SmO2 for sevoflurane, SNP, and NTG, respectively (P = 0.02 among groups). All tissue oxygen saturations recovered promptly after release of the aortic cross-clamp. For SmO2, the maximal relative changes were larger and the rate of decay was faster in the SNP group compared with the NTG group (Table 3).
AUC for oxygen saturation from each site is depicted in Figure 1. No differences were observed among the 3 treatment groups in AUC for left-sided and right-sided rScO2 (P = 0.74 and P = 0.17, respectively). For renal AUC, there was a difference between the NTG and the SNP group (P = 0.009). There were no differences in muscle AUC among the treatment groups (P = 0.05 for NTG versus sevoflurane, and P = 0.03 for NTG versus SNP). Right-sided rScO2 and MAP showed a poor correlation for NTG (r = −0.2, P = 0.93), whereas the correlation was borderline for sevoflurane (r = 0.44, P = 0.09) and SNP (r = 0.56, P = 0.04).
An effect of age was observed on the maximal relative decrease of SrO2 (unstandardized β = 0.06, 99% CI −0.02 to 0.14, P = 0.06) and SmO2 (unstandardized β = 0.07, 99% CI 0.01–0.13, P = 0.03). This effect was independent of the study product used (unstandardized β = 1.5, 99% CI −12.4 to 15.4, P = 0.76 for SrO2 and unstandardized β = 6.3, 99% CI −7.9 to 20.6, P = 0.23 for SmO2).
Analysis of hematocrit, blood gas partial pressures, and lactate levels performed 5 minutes after aortic cross-clamp removal is presented in Table 4. There were no differences among the treatment groups. In all patients, clinical recovery was uneventful. Postoperative lactate levels and blood creatinine levels were comparable among groups.
In this randomized, clinical study, the effects of blood pressure–regulating strategies with SNP, NTG, or sevoflurane on rScO2, SrO2, and SmO2 were investigated during aortic cross-clamping in children undergoing aortic coarctation repair. Although no differences in rScO2 values were observed among the 3 strategies, the mean differences in left-sided rScO2 among the 3 treatment groups was no more than 32%. Decreases in SrO2 and SmO2 were larger and had a faster rate of decay in SNP-treated patients. For both SNP and sevoflurane MAP-rScO2 dependence was higher than for NTG.
Effects on Cerebral Oxygen Saturation
In this study, aortic cross-clamping always involved temporary occlusion of the left carotid artery. This maneuver was associated with a variable response of the left-sided rScO2, ranging from a decrease to an increase in rScO2. CIs for pairwise comparisons between groups were wide. Although our study design did not allow us to comment on possible underlying mechanisms, it is conceivable that this phenomenon merely reflects the functional adequacy of the circle of Willis.
In a study on 18 patients undergoing aortic coarctation repair, Azakie et al.2 observed a pronounced decrease in left rScO2 in 2 patients treated with SNP, in whom the left carotid artery was clamped during the intervention. They attributed this finding to an SNP-induced disruption of cerebral autoregulation. However, because in that study no simultaneous recording of both left and right hemispheres was obtained, it cannot be determined whether this rScO2 decrease is the result of an agent-specific effect or rather a deficient circle of Willis.
We observed no significant differences in right rScO2 values among the different blood pressure–regulating strategies; however, with NTG treatment, changes in rScO2 were less dependent on changes in MAP than with SNP and sevoflurane. A higher correlation between MAP and rScO2 has been reported to be indicative of impaired cerebral autoregulation, whereas values around zero and negative values could be considered as representative of intact autoregulation.11,12 In line with this reasoning, the higher correlation between MAP and rScO2 in the SNP and sevoflurane groups compared with the NTG group would suggest that SNP and sevoflurane may interfere to a larger extent with cerebral autoregulation than NTG. This is in accordance with previous work reporting on dose-dependent impairment of cerebral autoregulation with SNP,13 whereas there was no significant impairment with NTG.14,15 Data on the effect of sevoflurane on cerebral autoregulation are controversial. It is generally assumed that cerebral autoregulation is maintained at low concentrations of sevoflurane, whereas higher doses seem to decrease autoregulatory capacity.16
Effects on Renal and Muscle Oxygen Saturation
Concerning the effects on peripheral tissue oxygen saturation, a larger and faster decrease in both SrO2 and SmO2 was observed in children treated with SNP. Previous studies have suggested that SNP-induced hypotension might worsen the impaired oxygen balance of tissues below the aortic cross-clamp.3–5 These findings could not be readily explained. Of interest, an experimental study on striated hamster muscle conducted by Endrich et al.17 demonstrated that SNP dilated preferentially precapillaries and caused a consistent increase in intravascular pressure within the venules. Consequently, the arteriolar-venular pressure gradient was reduced and functional capillary density decreased, leading to skeletal muscle tissue hypoxia. In contrast, NTG dilated both arterioles and venules, leaving the functional capillary density and local PO2 unchanged. Our findings are in accordance with the results of Endrich et al.17 and suggest that NTG may be preferable to SNP in terms of tissue oxygenation.
In all patients, both SrO2 and SmO2 declined to a plateau phase, which indicated that oxygen delivery no longer met metabolic oxygen requirements, likely resulting in anaerobic metabolism. The duration of the nadir of oxygenation has been demonstrated to be directly related to the extent of tissue injury.18,19 Sakamoto et al.18 demonstrated that nadir times of <25 minutes did not induce tissue injury. It can therefore be expected that the nadir times in our study were too short to translate into changes of biomarkers indicative for tissue injury, such as serum lactate, base excess, and creatinine levels.
The results of the present study should be interpreted within the constraints of the methodology. First, because of absence of evident adverse clinical events due to the short aortic cross-clamp times, the clinical implications of the current study on outcome remain to be determined. Second, the current study population comprised only young patients. Because the extent of collateral circulation has been shown to be age-related,10 the validity of the current results in older patients with a possibly more developed collateral circulation needs to be confirmed. Third, the reliability of NIRS to measure specific renal oxygen saturation can be questioned because of the uncertainty related to the depth of penetration of the near-infrared light in relation to the kidney. However, a number of studies have suggested that placement of an NIRS sensor over the flank might indeed reflect SrO2. Ortmann et al.20 demonstrated a strong correlation between flank NIRS values and renal vein saturation in children weighing <10 kg. Also, low renal tissue oxygen saturations measured with NIRS were associated with renal dysfunction after pediatric cardiac surgery21 and after aortic coarctation repair.22
In conclusion, although no significant differences were observed in rScO2 values among the different blood pressure–regulating strategies, mean differences in left-sided rScO2 among the 3 treatment groups was no more than 32%. With NTG treatment, changes in rScO2 were less dependent on changes in MAP than with SNP and sevoflurane. Decreases in SrO2 and SmO2 were larger and had a faster rate of decay in SNP-treated patients. Based on the lower MAP-rScO2 dependence and the smaller and slower decreases in SrO2 and SmO2, our data suggest that NTG might be preferable for blood pressure control during surgical procedures involving aortic cross-clamping.
Name: Annelies Moerman, MD.
Contribution: This author helped design the study, conduct the study, collect the data, analyze the data, and write the manuscript.
Attestation: Annelies Moerman attests to the integrity of the original data and the analysis reported in this manuscript, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Thierry Bové, MD.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Attestation: Thierry Bové attests to the integrity of the original data and the analysis reported in this manuscript, and approved the final manuscript.
Name: Katrien François, MD, PhD.
Contribution: This author helped design the study, conduct the study, and write the manuscript.
Attestation: Katrien François approved the final manuscript.
Name: Stefan Jacobs, MD.
Contribution: This author helped conduct the study.
Attestation: Stefan Jacobs approved the final manuscript.
Name: Isabel Deblaere, MD.
Contribution: This author helped conduct the study.
Attestation: Isabel Deblaere approved the final manuscript.
Name: Patrick Wouters, MD, PhD.
Contribution: This author helped design the study and write the manuscript.
Attestation: Patrick Wouters approved the final manuscript.
Name: Stefan De Hert, MD, PhD.
Contribution: This author helped analyze the data and write the manuscript.
Attestation: Stefan De Hert attests to the integrity of the original data and the analysis reported in this manuscript, and approved the final manuscript.
This manuscript was handled by: Charles W. Hogue, Jr., MD.
The authors are grateful to Marc De Buyzere for his valuable guidance and assistance regarding statistical review.
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© 2013 International Anesthesia Research Society
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