In a cohort of mostly elderly and high-risk patients we found that the average MAP at the LLA during CPB was 66 mmHg. There was much variability in the LLA, though, with a 95% prediction interval between 43 and 90 mmHg. We further found that predicting the MAP at the LLA during CPB based on clinical history and preoperative arterial blood pressure was imprecise. In contrast to clinical predictors, we found that the NIRS-based cerebral oximetry index was significantly associated with the MAP at the LLA. Women tended to have a lower MAP at the LLA than men while patients with a stroke tended to have a higher MAP at the autoregulation threshold than those without stroke.
The current understanding of cerebral blood flow autoregulation in patients during CPB is mostly based on data derived using 133
xenon washout or N2
O dilution methods.1,2,4,5,28,29
These studies were often limited to pooled data or to a limited number of discrete measurements made when CPB flow was maintained and MAP manipulated with vasoactive drugs. Based on these data, a basic tenet of patient management during CPB has been that a MAP as low as 20 mmHg to 55 mmHg may be tolerated since autoregulation is intact and CPB flow is relatively constant. 1,2,4,5,28,29
However, this practice was challenged by Gold et al6
who reported that targeting a MAP of 80 to 100 mmHg during CPB was associated with a lower combined frequency of stroke and myocardial outcomes than when MAP was targeted at 50 to 60 mmHg. The external validity of these results were questioned due to the small sample size (n=248) and an unexpectedly high rate of stroke in the control group (7.2%).7
Nonetheless, there is currently little evidence to guide clinicians on the most appropriate MAP targets during CPB. This may have implications for current practices that include increasing proportions of elderly patients with cerebrovascular disease.10,11
Continuous cerebral blood flow autoregulation monitoring as used in this study provides an individual estimate of autoregulation based on fluctuations in MAP that occur during the course of surgery. This approach allows perhaps for a more precise determination of the LLA than discrete and intermittent measurements. The continuous nature of the measurement is important as cerebral blood flow autoregulation is dynamic and potentially influenced by many perioperative perturbations, including rewarming from hypothermia, volatile anesthetics (dose dependently), and anemia.30,31
Our observations suggests that predicting the exact MAP target during CPB to remain above the LLA is difficult based on clinical history and preoperative blood pressure measurement. Although there was a positive relationship between the MAP at the LLA and systolic blood pressure (i.e., higher MAP at the LLA with increasing systolic blood pressure), this association was limited to patients with systolic blood pressure ≤ 160 mmHg and the association was less robust compared with cerebral oximetry index ≥ 0.5 (). The sensitivity of predicting the MAP at the LLA based on preoperative MAP had wide confidence intervals and low specificity (). Furthermore, the low area under the ROC curve suggests that factors other than preoperative MAP influence the ability to predict this end-point. Ultimately, the exact tolerance of error in predicting MAP during CPB will depend on the patient population. Our observations suggest that a MAP in the usual clinical range of 50 to 70 mmHg during CPB might result in cerebral blood flow being pressure passive in some patients predisposing to cerebral hypoperfusion.10,11
At the same time, maintaining empirically high MAP targets may unnecessarily expose some patients with a low LLA to higher cerebral blood flow potentially increasing cerebral embolic load and predisposing to cerebral edema.5,32
Transcranial Doppler monitoring during cardiac surgery is associated with many known limitations including the need to frequently readjust the transducer and interference from electric cautery. These limitations are particularly germane before CPB when continuous monitoring is difficult during harvest of the internal mammary artery when electrocautery use and patient repositioning are frequent. For this reason, we do not provide estimates of the LLA before CPB for comparing transcranial Doppler results with NIRS data. In contrast, NIRS output, and hence autoregulation monitoring, is continuous throughout surgery and it is not susceptible to the same limitations of transcranial Doppler. Thus, in clinical practice MAP targets derived from NIRS would be available before CPB and even after surgery when patient movement may limit transcranial Doppler monitoring.
We did not find a difference in the MAP at the LLA for patients with or without diabetes, hypertension, or prior stroke. These conditions have been suggested to result in a rightward shifted LLA.18-20
Our comparison group was not a normal control group, but rather included patients with cardiovascular disease and its associated endothelial dysfunction that results in abnormalities in microcirculatory process maintaining cerebral blood flow autoregulation.33
We did observe that patients suffering stroke had a higher MAP at the LLA compared with patients without a stroke (74±15 mmHg versus 66±12 mmHg, p=0.054). These findings are tempered, though, by the small number of patients in our study that does not allow for risk adjustments. Our use of arterial blood pressure measurement from the preoperative evaluation might not represent a true baseline measurement. This measurement, however, is what clinicians usually evaluate when planning perioperative care. Thus, our methods represent a pertinent clinical practice situation.
In our study we used a time-domain approach for cerebral blood flow monitoring that assumes that changes in transcranial Doppler-measured blood flow velocity over short periods of time result from changes in MAP. This method does not require assumptions of stationarity as with frequency domain methods (e.g., based on phase shifts, transfer functions) of cerebral blood flow autoregulation assessments that are not consistently present during surgery and in critical care settings.14
The signal-to-noise ratio with our approach, however, is less than with other cerebral blood flow autoregulation testing methods because the output (cerebral blood flow velocity) and input (MAP) contain both noise and autoregulation information. Time averaging of the data and focusing on slow wave fluctuations in cerebral blood flow velocity (0.003 to 0.04 Hz) are used to improve the signal-to-noise ratio. Changes in cerebral blood flow velocity in this frequency range are believed to represent autoregulatory compensatons to slow hemodynamic oscillations.34-36
Our results support our prior findings showing that NIRS can be exploited for autoregulation monitoring.16,24,37,38
In a piglet laboratory model we found that cerebral oximetry index was significantly correlated with cerebral blood flow autoregulation monitoring based on laser Doppler methods.24
In that study, and in an investigation of neurosurgical patients, NIRS waveforms at frequencies lower than 0.04 Hz had high coherence with laser Doppler or transcranial Doppler-measured cerebral blood flow velocity, respectively.24,35
We have found significant coherence between slow waves of cerebral blood flow velocity and NIRS in patients during CPB.16
These data together suggest that cerebral blood flow autoregulation monitoring is possible in patients during CPB using NIRS. Basing MAP targets during CPB on real-time cerebral blood flow autoregulation data, compared with the current standard of care of empirically derived targets, might ensure adequate cerebral blood flow during surgery and lead to improved neurological outcomes.
As mentioned, mean velocity index indicating the limits of autoregulation is likely to be between 0.25 and 0.5.14,21,24,39
We acknowledge that the use of a mean velocity index of ≥ 0.4 for defining the LLA is somewhat arbitrary. This is in part due to the nature of autoregulation whereby vasoreactivity responsible for mediating this response continues until extremely low blood pressure.14
That is, a discrete threshold where cerebral blood flow becomes completely blood pressure-passive is unlikely. Thus, the correlation between cerebral blood flow and MAP does not precipitously increase to values closer to 1 at some MAP. Rather, mean velocity index incrementally increases with declining MAP. Thus, our approach may have resulted in some error in depicting an exact MAP at the LLA if this occurred at a lower or higher mean velocity index in some patients. Regardless, the value of mean velocity index we chose was associated with delirium in patients with sepsis.35
The effects of nonpulsatile CPB flow on cerebral autoregulation are not known. Studies in animals did not show a convincing effect of nonpulsatile CPB on global cerebral blood flow or regional oxygen saturation.40
Further, the issue of nonpulsatile versus pulsatile CPB perfusion would likely affect autoregulation determinations by either the continuous methods we used or the intermittent measurements used with 133
xenon washout or the Kety-Smith method. Regardless, arterial blood pressure is rarely truly “nonpulsatile” during CPB due to small variations in blood pressure from the non-occlusive roller pump variation of flow. Finally, our methods use averaged blood pressure and cerebral blood flow velocity in the calculations that would reduce the influence of nonpulsatile CPB.
In conclusion, there is a wide range of MAP at the LLA in patients during CPB making estimating this target difficult. Real-time monitoring of autoregulation using cerebral oximetry index may provide a more rationale means for individualizing MAP during CPB.