Mitochondrial Oxygenation During Cardiopulmonary Bypass: A Pilot Study

Abstract

Objective: Adequate oxygenation is essential for the preservation of organ function during cardiac surgery and cardiopulmonary bypass (CPB). Both hypoxia and hyperoxia result in undesired outcomes, and a narrow window for optimal oxygenation exists. Current perioperative monitoring techniques are not always sufficient to monitor adequate oxygenation. The non-invasive COMET^® monitor could be a tool to monitor oxygenation by measuring the cutaneous mitochondrial oxygen tension (mitoPO₂). This pilot study examines the feasibility of cutaneous mitoPO₂ measurements during cardiothoracic procedures. Cutaneous mitoPO₂ will be compared to tissue oxygenation (StO₂) as measured by near-infrared spectroscopy.

Design and method: This single-center observational study examined 41 cardiac surgery patients requiring CPB. Preoperatively, patients received a 5-aminolevulinic acid plaster on the upper arm to enable mitoPO₂ measurements. After induction of anesthesia, both cutaneous mitoPO₂ and StO₂ were measured throughout the procedure. The patients were observed until discharge for the development of acute kidney insufficiency (AKI).

Results: Cutaneous mitoPO₂ was successfully measured in all patients and was 63.5 [40.0-74.8] mmHg at the surgery start and decreased significantly (p < 0.01) to 36.4 [18.4-56.0] mmHg by the end of the CPB run. StO₂ at the surgery start was 80.5 [76.8-84.3]% and did not change significantly. Cross-clamping of the aorta and the switch to non-pulsatile flow resulted in a median cutaneous mitoPO₂ decrease of 7 mmHg (p < 0.01). The cessation of the aortic cross-clamping period resulted in an increase of 4 mmHg (p < 0.01). Totally, four patients developed AKI and had a lower preoperative eGFR of 52 vs. 81 ml/min in the non-AKI group. The AKI group spent 32% of the operation time with a cutaneous mitoPO₂ value under 20 mmHg as compared to 8% in the non-AKI group.

Conclusion: This pilot study illustrated the feasibility of measuring cutaneous mitoPO₂ using the COMET^® monitor during cardiothoracic procedures. Moreover, in contrast to StO₂, mitoPO₂ decreased significantly with the increasing CPB run time. Cutaneous mitoPO₂ also significantly decreased during the aortic cross-clamping period and increased upon the release of the clamp, but StO₂ did not. This emphasized the sensitivity of cutaneous mitoPO₂ to detect circulatory and microvascular changes.

Keywords: acute kidney injury; cardiopulmonary bypass and maze procedure; ischemia; microcirculation; mitochondria; mitochondrial oxygenation.

Figure 1

Aortic cross-clamp data window preparation. The window time period is the same for the CABG cohort and the valve surgery cohort, such as 15 min after the start of extracorporeal circulation. In the CABG group, the flow is pulsatile in the data window, and in the valve surgery group, it is non-pulsatile, since the aortic cross-clamp has been set.

Figure 2

Patient study flowchart.

Figure 3

First and last four values during CPB, COMET^® cutaneous mitoPO₂ n = 41, ***p < 0.01, INVOS^® StO₂, n = 31, p = not significant (NS). Boxplot with median, IQR box, and whisker 1.5 times IQR.

Figure 4

(A) Distribution of cutaneous mitoPO₂ during CPB and (B) distribution of StO₂ during CPB, with the start of CPB at t = 0. Dots represent the mean value of patient-averaged cutaneous mitoPO₂ per 10-min window. Whiskers demonstrate the standard deviation. Bars represent the number of patients.

Figure 5

Cutaneous mitoPO₂ values before and after aortic clamping and cutaneous mitoPO₂ values before and after the release of aortic clamping. WU test paired p < 0.01***.

Figure 6

Comparison between valve surgery aortic cross-clamp period and CABG non-aortic cross-clamp period. An average of the 20-min data window after the extracorporeal circulation has been running for 15 min per patient. Mean SD plot of cutaneous mitoPO₂. *indicates a statistically significant difference p < 0.05.

Figure 7

Example of minutes below threshold calculation. The dots are cutaneous mitoPO₂ values, and the dashed line is the threshold set at 20 mmHg. In this case, the cutaneous mitoPO₂ was below the threshold for 13 min.

Figure 8

(A) Absolute time within cutaneous mitoPO₂ ranges for AKI (n = 4) patients and non-AKI (n = 37) patients. The cutaneous mitoPO₂ ranges were below 20 mmHg, between 20 and 40 mmHg, and above 40 mmHg. Boxplot with median, IQR box, and whisker 1.5 times IQR, and outliers are not shown. (B) Time spent within a range as a proportion of CPB/extracorporeal circulation duration. Proportion is achieved by dividing the number of minutes below the threshold by CPB duration.