C. S.E. Bulte

Diabetes, perioperative ischaemia and volatile anaesthetics: consequences of derangements in myocardial substrate metabolism

Volatile anaesthetics exert protective effects on the heart against perioperative ischaemic injury. However, there is growing evidence that these cardioprotective properties are reduced in case of type 2 diabetes mellitus. A strong predictor of postoperative cardiac function is myocardial substrate metabolism. In the type 2 diabetic heart, substrate metabolism is shifted from glucose utilisation to fatty acid oxidation, resulting in metabolic inflexibility and cardiac dysfunction. The ischaemic heart also loses its metabolic flexibility and can switch to glucose or fatty acid oxidation as its preferential state, which may deteriorate cardiac function even further in case of type 2 diabetes mellitus.Recent experimental studies suggest that the cardioprotective properties of volatile anaesthetics partly rely on changing myocardial substrate metabolism. Interventions that target at restoration of metabolic derangements, like lifestyle and pharmacological interventions, may therefore be an interesting candidate to reduce perioperative complications. This review will focus on the current knowledge regarding myocardial substrate metabolism during volatile anaesthesia in the obese and type 2 diabetic heart during perioperative ischaemia.

Reproducibility of non-standardised autonomic function testing in the pre-operative assessment screening clinic*

By convention, autonomic function tests are undertaken under standard test conditions that limit their implementation during routine pre‐operative assessment. We therefore evaluated the comparability of autonomic function tests under both non‐standardised and standardised test conditions in 20 healthy male subjects. Autonomic function was assessed using an ECG monitor and a continuous non‐invasive blood pressure measurement device. Under non‐standardised conditions, intraclass correlation for heart rate variability analysis was good for the low and high frequency bands (0.87; 95% CI 0.58–0.96 and 0.83; 95% CI 0.56–0.94, respectively), but moderate (0.65; 95% CI 0.14–0.86) for the very low frequency band; reproducibility was high for the expiration/inspiration ratio (0.89; 95% CI 0.71–0.96), Valsalva ratio (0.76; 95% CI 0.37–0.91) and handgrip test (0.76; 95% CI 0.35–0.91) (all p < 0.05) but was low for the response to quick standing. Reproducibility under standardised conditions was comparable to the above values. We demonstrated that reproducibility for most autonomic tests under non‐standardised conditions is acceptable and suggest that implementation of these tests during pre‐operative assessment may be feasible.

General anesthesia with sevoflurane decreases myocardial blood volume and hyperemic blood flow in healthy humans

BACKGROUND:Preservation of myocardial perfusion during general anesthesia is likely important in patients at risk for perioperative cardiac complications. Data related to the influence of general anesthesia on the normal myocardial circulation are limited. In this study, we investigated myocardial microcirculatory responses to pharmacological vasodilation and sympathetic stimulation during general anesthesia with sevoflurane in healthy humans immediately before surgical stimulation. METHODS:Six female and 7 male subjects (mean age 43 years, range 28–61) were studied at baseline while awake and during the administration of 1 minimum alveolar concentration sevoflurane. Using myocardial contrast echocardiography, myocardial blood flow (MBF) and microcirculatory variables were assessed at rest, during adenosine-induced hyperemia, and after cold pressor test–induced sympathetic stimulation. MBF was calculated from the relative myocardial blood volume multiplied by its exchange frequency (&bgr;) divided by myocardial tissue density (&rgr;T), which was set at 1.05 g·mL−1. RESULTS:During sevoflurane anesthesia, MBF at rest was similar to baseline values (1.05 ± 0.28 vs 1.05 ± 0.32 mL·min−1·g−1; P = 0.98; 95% confidence interval [CI], −0.18 to 0.18). Myocardial blood volume decreased (P = 0.0044; 95% CI, 0.01–0.04) while its exchange frequency (&bgr;) increased under sevoflurane anesthesia when compared with baseline. In contrast, hyperemic MBF was reduced during anesthesia compared with baseline (2.25 ± 0.5 vs 3.53 ± 0.7 mL·min−1·g−1; P = 0.0003; 95% CI, 0.72–1.84). Sympathetic stimulation during sevoflurane anesthesia resulted in a similar MBF compared to baseline (1.53 ± 0.53 and 1.55 ± 0.49 mL·min−1·g−1; P = 0.74; 95% CI, −0.47 to 0.35). CONCLUSIONS:In otherwise healthy subjects who are not subjected to surgical stimulation, MBF at rest and after sympathetic stimulation is preserved during sevoflurane anesthesia despite a decrease in myocardial blood volume. However, sevoflurane anesthesia reduces hyperemic MBF, and thus MBF reserve, in these subjects.

Contrast-enhanced ultrasound for myocardial perfusion imaging.

Ultrasound contrast agents are gas-filled microbubbles that enhance visualization of cardiac structures, function and blood flow during contrast-enhanced ultrasound (CEUS). An interesting cardiovascular application of CEUS is myocardial contrast echocardiography, which allows real-time myocardial perfusion imaging. The intraoperative use of this technically challenging imaging method is limited at present, although several studies have examined its clinical utility during cardiac surgery in the past. In the present review we provide general information on the basic principles of CEUS and discuss the methodology and technical aspects of myocardial perfusion imaging.

Level of agreement between heart rate variability and pulse rate variability in healthy individuals.

Background and objective According to international standards, autonomic function is assessed by heart rate variability (HRV) calculated from R–R intervals obtained with an electrocardiogram (ECG). However, intra-operative movement artefacts and electrical interference may complicate R-wave detection. Pulse rate variability (PRV) derived from continuous blood pressure measurements may provide a feasible alternative for HRV. We aimed to investigate the level of agreement between PRV and traditional HRV using a novel beat-to-beat non-invasive blood pressure monitoring device. Methods In this prospective observational study, R–R intervals and non-invasive blood pressure waveforms were recorded simultaneously from 20 healthy male individuals at rest. HRV and PRV were analysed offline by spectral analysis, which divides the signal into its composing frequencies. Spearmans correlation coefficient, intra-class correlation coefficients and Bland–Altman analysis were used to study the level of agreement between HRV and PRV. Results The correlation coefficient between HRV and PRV was 0.99 (P < 0.001). Level of agreement was excellent with a mean difference of 1% in the very low frequency and low-frequency band and 14% in the high-frequency band. Reliability of both HRV and PRV was moderate to high. Conclusion Our data show that PRV derived from non-invasive blood pressure waveforms corresponds well with traditional HRV derived from ECG. These results indicate that under standard conditions, blood pressure waveforms may replace HRV in healthy individuals and that the use of PRV in the peri-operative setting should be further evaluated.

High fat diet-induced glucose intolerance impairs myocardial function, but not myocardial perfusion during hyperaemia: a pilot study

BackgroundGlucose intolerance is a major health problem and is associated with increased risk of progression to type 2 diabetes mellitus and cardiovascular disease. However, whether glucose intolerance is related to impaired myocardial perfusion is not known. The purpose of the present study was to study the effect of diet-induced glucose intolerance on myocardial function and perfusion during baseline and pharmacological induced hyperaemia.MethodsMale Wistar rats were randomly exposed to a high fat diet (HFD) or control diet (CD) (n = 8 per group). After 4 weeks, rats underwent an oral glucose tolerance test. Subsequently, rats underwent (contrast) echocardiography to determine myocardial function and perfusion during baseline and dipyridamole-induced hyperaemia (20 mg/kg for 10 min).ResultsFour weeks of HFD feeding resulted in glucose intolerance compared to CD-feeding. Contractile function as represented by fractional shortening was not altered in HFD-fed rats compared to CD-fed rats under baseline conditions. However, dipyridamole increased fractional shortening in CD-fed rats, but not in HFD-fed rats. Basal myocardial perfusion, as measured by estimate of perfusion, was similar in CD- and HFD-fed rats, whereas dipyridamole increased estimate of perfusion in CD-fed rats, but not in HFD-fed rats. However, flow reserve was not different between CD- and HFD-fed rats.ConclusionsDiet-induced glucose intolerance is associated with impaired myocardial function during conditions of hyperaemia, but myocardial perfusion is maintained. These findings may result in new insights into the effect of glucose intolerance on myocardial function and perfusion during hyperaemia.

Beat-to-beat hemodynamic monitoring during electroconvulsive therapy.

Objectives: Rapid parasympathetic and sympathetic hemodynamic effects during electroconvulsive therapy (ECT) may pose vulnerable patients to significant risk for cardiovascular complications. Here, we evaluated the clinical feasibility of noninvasive beat-to-beat arterial blood pressure (BP) measurements in patients undergoing ECT. Methods: Beat-to-beat hemodynamic effects were measured with a noninvasive BP monitor in 24 individual patients undergoing ECT during general anesthesia. Heart rate, systolic (SBP), and diastolic BP (DBP) as well as cardiac output (CO) were measured continuously. A significant increase in pulse rate and/or BP was treated with intermittent administration of esmolol and ketanserin. Data are presented as mean ± SD. Results: The ECT stimulus induced a transient drop in BP and pulse rate, followed by a sharp rise in both parameters. The parasympathetic phase lasted 17 ± 9 seconds and was characterized by a drop in heart rate from 89 ± 15 to 42 ± 24 beats per minute, in SBP from 143 ± 22 to 91 ± 31 mm Hg, in DBP from 82 ± 13 to 54 ± 22 mm Hg, and in CO from 5.7 ± 2.3 to 1.4 ± 1.0 L/min, respectively. During the subsequent sympathetic phase, the heart rate increased to 125 ± 26 beats per minute, the SBP to 192 ± 33 mm Hg, the DBP to 113 ± 21 mm Hg, and the CO to 7.4 ± 4.3 L/min. The time interval between the lowest and highest SBP was 60 ± 48 seconds. Conclusions: Noninvasive beat-to-beat BP measurements are feasible during ECT and may be used to guide rapid therapeutic interventions during ECT-induced hemodynamic effects.

The impact of autonomic dysfunction on peri-operative cardiovascular complications

Cardiovascular autonomic neuropathy is frequently observed in patients with diabetes mellitus. As anaesthesia has a marked effect on peri‐operative autonomic function, the interplay between diabetic neuropathy and anaesthesia may result in unexpected haemodynamic instability during surgery. The objective of this literature review was to examine the association of cardiovascular autonomic neuropathy with peri‐operative cardiovascular complications. We searched PubMed for articles with search elements of autonomic dysfunction [MeSH] AND anaesthesia [MeSH] AND complications [MeSH]. Depending on the type of anaesthesia, the presence of cardiovascular autonomic neuropathy in surgical patients can markedly affect peri‐operative haemodynamics and postoperative recovery. Pre‐operative testing of the extent of autonomic dysfunction in particular populations, like diabetics, may contribute to a reduction in haemodynamic instability and cardiovascular complications. Non‐invasive diagnostic methods assessing autonomic function may be an important tool during pre‐operative risk assessment.

Myocardial blood flow under general anaesthesia with sevoflurane in type 2 diabetic patients: a pilot study

BackgroundIn type 2 diabetic patients, cardiac events in the perioperative period may be associated with diminished myocardial vasomotor function and endothelial dysfunction. The influence of sevoflurane anaesthesia on myocardial endothelial dysfunction in type 2 diabetic mellitus is investigated in this pilot study.MethodsSix males with type 2 diabetes mellitus and eight healthy controls were included. Using myocardial contrast echocardiography, myocardial blood flow (MBF) was measured at rest, during adenosine-induced hyperaemia (endothelium-independent vasodilation) and after sympathetic stimulation by the cold pressor test (endothelium-dependent vasodilation). Measurements were performed before and after induction of sevoflurane anaesthesia.ResultsSevoflurane anaesthesia decreased resting MBF in diabetics but not in controls (P = 0.03), while baseline MBF did not differ between diabetics and controls. Without anaesthesia, adenosine-induced hyperaemia increased MBF in both groups compared to resting values. Adenosine combined with sevoflurane resulted in a lower hyperaemic MBF in both groups compared to no anaesthesia. Differences in MBF in response to adenosine before and after sevoflurane administration were larger in diabetic patients, however not statistically significant in this pilot group (P = 0.08). Myocardial blood flow parameters after the cold pressor test were not different between groups.ConclusionThese pilot data in type 2 diabetic patients show that sevoflurane anaesthesia decreases resting myocardial blood flow compared to healthy controls. Further, we observed a trend towards a lower endothelium-independent vasodilation capacity in diabetic patients under sevoflurane anaesthesia. Endothelium-dependent vasodilation was not affected by sevoflurane in diabetic patients. These data provide preliminary insight into myocardial responses in type 2 diabetic patients under general anaesthesia.Trial registrationhttp://www.clinicialtrials.gov,NCT00866801

Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats

Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.