Eric P. van Dongen

Impact of left heart bypass on the results of thoracoabdominal aortic aneurysm repair.

BACKGROUND This study evaluated the role of left heart bypass on the results of thoracoabdominal aortic aneurysm (TAAA) operations. METHODS Two hundred fifty-eight patients had surgical repair of a thoracoabdominal aortic aneurysm between 1981 and 1998 using the inlay technique. Simple cross-clamping was used in 47.7% and left heart bypass (atriodistal) in 52.3%. Further surgical technique was identical: liberal intercostal or lumbar artery reimplantation, cerebrospinal fluid drainage (since 1989), administration of a renal cooling solution, permissive mild hypothermia, and no pharmacologic protection. Both univariate and multivariate analysis were used. RESULTS The hospital mortality rate was 10.1% overall: 14.6% in the cross-clamp group, and 5.9% in the bypass group (p = 0.02). The risk of hospital death increased with aneurysm rupture (odds ratio 5.6) and when the patient needed postoperative dialysis (odds ratio 7.5). The use of left heart bypass had a mild protective effect on hospital death (odds ratio 0.56). The incidence of postoperative renal failure requiring dialysis was 8.3% overall: 10.9% in the cross-clamp group, and 5.9% in the bypass group (p = 0.16). After multivariate analysis, a longer operative procedure (odds ratio 1.01 per minute) and a longer reappearance time of blue dye in the urine (odds ratio 1.05 per minute) increased the risk of dialysis, whereas the use of atriodistal bypass reduced that risk (odds ratio 0.08). Paraplegia or paraparesis occurred in 10.9% of patients overall: 13.2% in the cross-clamp group, and 8.8% in the bypass group (p = 0.27). After logistic regression, rupture increased the risk of paraplegia or paraparesis (odds ratio 3.2) and dissection reduced it (odds ratio 0.23). CONCLUSIONS The use of atriodistal bypass is beneficial in patients who had thoracoabdominal aortic aneurysm repair. Hospital mortality rates, postoperative dialysis, and paraplegia/paraparesis were reduced.

The influence of nitrous oxide to supplement fentanyl/low-dose propofol anesthesia on transcranial myogenic motor-evoked potentials during thoracic aortic surgery

OBJECTIVE Intraoperative monitoring of myogenic motor evoked potentials to transcranial electrical stimulation (tc MEPs) is a new method to assess the integrity of the motor pathways. The authors studied the effects of 50% nitrous oxide (N2O) and a low-dose propofol infusion on tc MEPs paired electrical stimulation during fentanyl anesthesia with partial neuromuscular blockade. DESIGN Cross-over study. SETTING St Antonius Hospital, Nieuwegein, The Netherlands. PARTICIPANTS Ten patients scheduled to undergo surgery on the thoracoabdominal aorta were studied; 6 women aged 54 to 69 years and 4 men aged 68 to 77 years. INTERVENTIONS After achieving a stable anesthetic state and before surgery, tc MEPs were recorded during four 15-minute periods: (I) air/oxygen (O2; F(I)O2 = 50%); propofol target blood concentration, 0.5 microg/mL; (II) N2O/O2 (F(I)O2 = 50%); propofol target blood concentration, 0.5 microg/mL; (III) N2O/O2 (F(I)O2 = 50%; propofol target blood concentration, 1.0 microg/mL; and (IV) air/O2 (F(I)O2 = 50%); propofol target blood concentration, 1.0 microg/mL. MEASUREMENTS AND MAIN RESULTS Tc MEPs were recorded from the right extensor digitorum communis muscle and the right tibialis anterior muscle. The right thenar muscle was used for recording the level of relaxation; the T1 response was maintained at 40% to 70% of the control compound muscle action potential. There was no significant difference in onset latency among the four phases. The addition of N2O and doubling the target propofol infusion to 1.0 microg/mL resulted in a 40% to 50% reduction of tc MEP amplitude recorded in the extensor digitorum communis muscle and tibialis anterior muscle (p < 0.01). During each phase, tc MEPs could be elicited and interpreted, except in one patient, in whom no tc MEPs could be elicited in the leg because of technical problems. CONCLUSION The data indicate that tc MEP monitoring is feasible during low-dose propofol, fentanyl/50% N2O in 02 anesthesia and partial neuromuscular blockade.

Within-patient variability of myogenic motor-evoked potentials to multipulse transcranial electrical stimulation during two levels of partial neuromuscular blockade in aortic surgery

UNLABELLED Intraoperative recording of myogenic motor responses evoked by transcranial electrical stimulation (tcMEPs) is a method of assessing the integrity of the motor pathways during aortic surgery. To identify conditions for optimal spinal cord monitoring, we investigated the effects of manipulating the level of neuromuscular blockade (T1 response of the train-of-four (TOF) stimulation 5%-15% versus T1 response 45%-55% of baseline), as well as the number of transcranial pulses (two versus six stimuli) on the within-patient variability and amplitude of tcMEPs. Ten patients (30-76 yr) scheduled to undergo surgery on the thoracic and thoracoabdominal aorta were studied. After achieving a stable anesthetic state and before surgery, 10 tcMEPs were recorded from the right extensor digitorum communis muscle and the right tibialis anterior muscle in response to two-pulse and six-pulse transcranial electrical stimulation with an interstimulus interval of 2 ms during two levels of neuromuscular blockade. The right thenar eminence was used for recording the level of relaxation. The tcMEP amplitude using the six-pulse paradigm was larger (P < 0.01; leg and arm) compared with the amplitude evoked by two-pulse stimulation during both levels of relaxation. The within-patient variability, expressed as median coefficient of variation, was less when six-pulse stimulation was used. At a T1 response of 45%-55% of baseline, larger, less variable tcMEPs were recorded than at a T1 response of 5%-15%. Our results suggest that the best quality of tcMEP signals (tibialis anterior muscle) is obtained when the six-pulse paradigm is used with a stable level of muscle relaxation (the first twitch of the TOF-thenar eminence-at 45%-55% of baseline). IMPLICATIONS This study shows that six-pulse (rather than two-pulse) transcranial electrical stimulation during a stable anesthetic state and a stable neuromuscular blockade aimed at 45%-55% (rather than 5%-15%) of baseline provides reliable and recordable muscle responses sufficiently robust for spinal cord monitoring in aortic surgery.

Population Pharmacokinetics and Pharmacodynamics of Propofol in Morbidly Obese Patients

AbstractBackground and Objectives: In view of the increasing prevalence of morbidly obese patients, the influence of excessive total bodyweight (TBW) on the pharmacokinetics and pharmacodynamics of propofol was characterized in this study using bispectral index (BIS) values as a pharmacodynamic endpoint. Methods: A population pharmacokinetic and pharmacodynamic model was developed with the nonlinear mixed-effects modelling software NONMEM VI, on the basis of 491 blood samples from 20 morbidly obese patients (TBW range 98–167 kg) and 725 blood samples from 44 lean patients (TBW range 55–98 kg) from previously published studies. In addition, 2246 BIS values from the 20 morbidly obese patients were available for pharmacodynamic analysis. Results: In a three-compartment pharmacokinetic model, TBW proved to be the most predictive covariate for clearance from the central compartment (CL) in the 20 morbidly obese patients (CL 2.33L/min × [TBW/70]^[0.72]). Similar results were obtained when the morbidly obese patients and the 44 lean patients were analysed together (CL 2.22 L/min × [TBW/70]^[0.67]). No covariates were identified for other pharmacokinetic parameters. The depth of anaesthesia in the morbidly obese patients was adequately described by a two-compartment biophase-distribution model with a sigmoid maximum possible effect (Emax) pharmacodynamic model (concentration at half-maximum effect [EC50] 2.12 mg/L) without covariates. Conclusion: We developed a pharmacokinetic and pharmacodynamic model of propofol in morbidly obese patients, in which TBW proved to be the major determinant of clearance, using an allometric function with an exponent of 0.72. For the other pharmacokinetic and pharmacodynamic parameters, no covariates could be identified.

Microcirculatory Imaging in Cardiac Anesthesia: Ketanserin Reduces Blood Pressure But Not Perfused Capillary Density

OBJECTIVES It has become possible to image the human microcirculation at the bedside using sidestream dark field (SDF) imaging. This may help the clinician when correlation between global and microvascular hemodynamics may not be straightforward. Ketanserin, a serotonin and alpha-1 adrenoceptor antagonist, is used in some countries to treat elevated blood pressure after extracorporeal circulation. This might hamper microcirculatory perfusion. Conversely, it is also conceivable that microcirculatory flow is maintained or improved as a result of flow redistribution. In order to introduce SDF imaging in cardiac anesthesia, the authors set out to directly observe the sublingual microcirculation in this setting. DESIGN An observational study. SETTING A large teaching hospital. PARTICIPANTS Mechanically ventilated patients with elevated arterial blood pressure immediately after extracorporeal circulation (ECC). INTERVENTION An intravenous bolus of ketanserin, 0.15 mg/kg. MEASUREMENTS AND MAIN RESULTS Five minutes before and 10 minutes after ketanserin administration, global hemodynamic variables were recorded. In addition, the authors used SDF imaging to record video clips of the microcirculation. Analysis of these allowed for quantification of microvascular hemodynamics including determination of perfused vessel density (PVD) and microcirculatory flow index (MFI). After ketanserin administration, there was a significant reduction in systolic arterial blood pressure (129 +/- 9 to 100 +/- 15 mmHg, p = 0.0001). At the level of the microcirculation, the mean MFI did not change significantly for small (diameter <20 microm, 2.79 [interquartile range, 1.38-3] to 2.38 [1.88-2.75], p = 0.62) or large (diameter >20 microm, 2.83 [1.4-3] to 2.67 [0.35-2.84] p = 1.0) vessels. There was a significant increase in mean PVD for large vessels (1.23 +/- 0.63 to 1.70 +/- 79 mm(-1), p = 0.017) but not for small vessels (5.59 +/- 2.60 to 5.87 +/- 1.22 mm(-1), p = 0.72) where red blood cell flow was maintained. CONCLUSIONS SDF imaging clearly showed a discrepancy between global and microvascular hemodynamics after the administration of ketanserin for elevated blood pressure after ECC. Ketanserin effectively lowers arterial blood pressure. However, capillary perfusion is maintained at a steady value. Both effects may be explained by an increase in shunting in the larger vessels of the microcirculation.

Risk factors for chronic thoracic pain after cardiac surgery via sternotomy

OBJECTIVE This study examines the influence of patient demographics and peri- and postoperative (<7 days) characteristics on the incidence of chronic thoracic pain 1 year after cardiac surgery. The impact of chronic thoracic pain on daily life is also documented. METHODS A prospective cohort study of 146 patients admitted to the intensive care unit after cardiac surgery via sternotomy was carried out. Pain scores (numeric rating scale 0-10) were recorded during the first 7 postoperative days. One year later, a questionnaire was used to evaluate the incidence in the 2 preceding weeks of chronic thoracic pain (numeric rating scale >0) associated with the primary surgery. RESULTS One year after surgery, 42 (35%) of the 120 responding patients reported chronic thoracic pain. Multivariate regression analysis of patient characteristics revealed that non-elective surgery, re-sternotomy, severe pain (numeric rating scale ≥ 4) on the third postoperative day, and female gender were all independent predictors of chronic thoracic pain. In addition, the chronic sufferers reported more sleep disturbances and more frequent use of analgesics than their cohorts. CONCLUSIONS We have identified a number of factors correlated with persistent thoracic pain following cardiac surgery with sternotomy. Awareness of these predictors may be useful for further research concerning both the prevention and treatment of chronic thoracic pain, thereby potentially ameliorating the postoperative quality of life of a significant proportion of patients. Meanwhile, chronic thoracic pain should be discussed preoperatively with patients at risk so that they are truly informed about possible consequences of the surgery.

Withdrawing intra-aortic balloon pump support paradoxically improves microvascular flow

IntroductionThe Intra-Aortic Balloon Pump (IABP) is frequently used to mechanically support the heart. There is evidence that IABP improves microvascular flow during cardiogenic shock but its influence on the human microcirculation in patients deemed ready for discontinuing IABP support has not yet been studied. Therefore we used sidestream dark field imaging (SDF) to test our hypothesis that human microcirculation remains unaltered with or without IABP support in patients clinically ready for discontinuation of mechanical support.MethodsWe studied 15 ICU patients on IABP therapy. Measurements were performed after the clinical decision was made to remove the balloon catheter. We recorded global hemodynamic parameters and performed venous oximetry during maximal IABP support (1:1) and 10 minutes after temporarily stopping the IABP therapy. At both time points, we also recorded video clips of the sublingual microcirculation. From these we determined indices of microvascular perfusion including perfused vessel density (PVD) and microvascular flow index (MFI).ResultsCeasing IABP support lowered mean arterial pressure (74 ± 8 to 71 ± 10 mmHg; P = 0.048) and increased diastolic pressure (43 ± 10 to 53 ± 9 mmHg; P = 0.0002). However, at the level of the microcirculation we found an increase of PVD of small vessels <20 μm (5.47 ± 1.76 to 6.63 ± 1.90; P = 0.0039). PVD for vessels >20 μm and MFI for both small and large vessels were unaltered. During the procedure global oxygenation parameters (ScvO2/SvO2) remained unchanged.ConclusionsIn patients deemed ready for discontinuing IABP support according to current practice, SDF imaging showed an increase of microcirculatory flow of small vessels after ceasing IABP therapy. This observation may indicate that IABP impairs microvascular perfusion in recovered patients, although this warrants confirmation.

The relationship between evoked potentials and measurements of S-100 protein in cerebrospinal fluid during and after thoracoabdominal aortic aneurysm surgery.

OBJECTIVE This study was performed to correlate the changes in concentration of S-100 protein in the cerebrospinal fluid (CSF) during and after thoracoabdominal aortic aneurysm (TAAA) surgery with the results of somatosensory and motor evoked potential monitoring. METHODS The study was designed as a prospective study at St Antonius Hospital in Nieuwegein, The Netherlands. The participants were 19 patients who were undergoing elective TAAA surgery. CSF samples for analysis of S-100 protein were drawn after the induction of anesthesia, during the cross-clamp period of the critical aortic segment, after 5 minutes of reperfusion of this segment, during the closure of the skin, and 24 hours after the closure of the skin. In all the patients, continuous intraoperative recording of myogenic motor potentials evoked by transcranial electrical stimulation (tcMEP) and somatosensory potentials evoked by stimulation of the posterior tibial nerve took place to monitor the integrity of the spinal cord. The operative technique consisted of staged or sequential clamping to maximize the beneficial effect of the distal perfusion by the left heart bypass, continuous CSF drainage to keep the CSF pressure below 10 mm Hg, and moderate hypothermia (32 degrees C rectal temperature). We correlated the measured concentrations of S-100 protein in CSF with the results of evoked potential monitoring during surgery and the number of intercostals reimplanted and oversewn. RESULTS In all the patients, the concentration of S-100 protein was increased in CSF. The highest concentration of S-100 protein was found in the CSF sample taken 5 minutes after reperfusion of the critical aortic segment. There was a good (negative) correlation between the changes in S-100 protein in CSF and the changes in motor evoked potential monitoring during the cross-clamp period. The best (negative) correlation was detected between the S-100 protein elevation in the CSF sample drawn 5 minutes after reperfusion and the tcMEP amplitude reduction during clamping (r = -0.73; P =.007). No relation was found between the S-100 protein dynamics in CSF and somatosensory evoked potential monitoring. A positive (r = 0.58; P =.05) correlation was found between the change in tcMEP amplitude during clamping and the number of reattached intercostals. A moderate to good (r = -0.5 to -0.7; P <.05) correlation between the number of reattached intercostals and the changes in S-100 protein concentration in CSF during TAAA surgery was found. Our data show that transient elevations in S-100 protein after cross clamping are larger in those patients with marked decrease in tcMEP from baseline during the cross-clamp period. CONCLUSION A correlation is shown between an increasing concentration of S-100 protein in CSF and a reduction in tcMEP amplitude during cross clamping of the aorta. The S-100 protein in CSF seems to be a marker of potential clinical value in the evaluation of the effects of procedures to detect and reduce spinal cord ischemia.

Myocardial oxidative stress, and cell injury comparing three different techniques for coronary artery bypass grafting

OBJECTIVE Oxidative stress as a result of reperfusion injury is a known causative factor of cardiac muscle injury. In the peripheral blood as well in the coronary sinus, oxidative stress parameters and cardiac biomarkers were measured to investigate the different levels of oxidative stress during three different CABG techniques; MCABG (with minimal prime volume and warm blood cardioplegia) that was newly introduced in our hospital, versus OPCAB, versus our current standard, conventional CABG (CCABG, consisting of high volume prime and cold crystalloid cardioplegia). Concomitantly, cardiac biomarkers were measured to detect myocardial cell injury. METHODS Thirty patients scheduled for CABG with the intention to treat three-vessel disease were randomly assigned for CCABG, MCABG or OPCAB. Perioperatively, plasma levels of malondialdehyde (MDA) as a marker of oxidative stress, and the allantoin/uric acid ratio (A/U ratio) as a marker of antioxidant activity were measured in the ascending aorta (Aa), and in the coronary sinus (Cs), simultaneously. Additionally peripheral (Aa) blood levels of heart fatty acid binding protein (HFABP), troponin T, CPK and CKMB as markers of myocardial injury were obtained. RESULTS The MCABG group had significantly lower MDA levels in the Cs compared to the CCABG group, respectively, to the OPCAB group (p=0.04 and p=0.03). At all time points the A/U ratio in the CCABG group remained significantly higher in the Cs as well in the Aa samples compared to the MCABG and the OPCAB group (p<0.001, respectively, p<0.001, for both groups). HFABP and troponin T showed consistent curves compared to the CPK figure over time in all groups. CONCLUSION In this study coronary sinus blood levels of oxidative stress parameters were consistently higher compared to peripheral blood levels. The levels were lowest in the MCABG study group. In this group also the lowest levels cardiac biomarkers of myocardial injury were found.

Normal serum concentrations of S-100 protein and changes in cerebrospinal fluid concentrations of S-100 protein during and after thoracoabdominal aortic aneurysm surgery: Is S-100 protein a biochemical marker of clinical value in detecting spinal cord ischemia?

PURPOSE This study was performed to determine the concentration of S-100 protein in serum and in the cerebrospinal fluid (CSF) during and 24 hours after thoracoabdominal aortic aneurysm repair. METHODS This prospective study was performed at St. Antonius Hospital in Nieuwegein, The Netherlands. Eight patients who underwent elective thoracoabdominal aortic surgery participated in the study. Arterial blood and CSF samples for analysis of S-100 protein were drawn after induction of anesthesia, during the cross-clamp period of the critical segment, after 5 minutes of reperfusion, during the closure of the skin, and 24 hours after closure of the skin. RESULTS No increase in S-100 protein concentration could be detected in serum (< 0.2 microg/L). The S-100 protein concentration in CSF increased during the procedure in all patients (4.2 +/- 3.1 microg/L). However, in one patient, who became paraplegic, the S-100 protein concentration in CSF increased even further after 24 hours (10 microg/L). CONCLUSIONS The preliminary results suggest that S-100 protein in CSF may be a marker of clinical value in evaluating the effects of measures to detect and reduce spinal cord ischemia.