Publications by authors named "Leon P Aarts"

37 Publications

Biventricular function in exercise during autonomic (thoracic epidural) block.

Eur J Appl Physiol 2021 May 22;121(5):1405-1418. Epub 2021 Feb 22.

Department of Anesthesia, University Hospitals Ghent, Ghent, Belgium.

Background: Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia (TEA) was previously shown to reduce right and left ventricular systolic function and effective pulmonary arterial elastance. At conditions of constant paced heart rate, cardiac output and systemic hemodynamics were unchanged. In this study, we further investigated the effect of cardiac sympathicolysis during physical stress and increased oxygen demand.

Methods: In a cross-over design, 12 patients scheduled to undergo thoracic surgery performed dynamic ergometric exercise tests with and without TEA. Hemodynamics were monitored and biventricular function was measured by transthoracic two-dimensional and M-mode echocardiography, pulsed wave Doppler and tissue Doppler imaging.

Results: TEA attenuated systolic RV function (TV S': - 21%, P < 0.001) and LV function (MV S': - 14%, P = 0.025), but biventricular diastolic function was not affected. HR (- 11%, P < 0.001), SVI (- 15%, P = 0.006), CI (- 21%, P < 0.001) and MAP (- 12%, P < 0.001) were decreased during TEA, but SVR was not affected. Exercise resulted in significant augmentation of systolic and diastolic biventricular function. During exercise HR, SVI, CI and MAP increased (respectively, + 86%, + 19%, + 124% and + 17%, all P < 0.001), whereas SVR decreased (- 49%, P < 0.001). No significant interactions between exercise and TEA were found, except for RPP (P = 0.024) and MV E DT (P = 0.035).

Conclusion: Cardiac sympathetic blockade by TEA reduced LV and RV systolic function but did not significantly blunt exercise-induced increases in LV and RV function. These data indicate that additional mechanisms besides those controlled by the cardiac sympathetic nervous system are involved in the regulation of cardiac function during dynamic exercise. Trial registration Clinical trial registration: Nederlands Trial Register, NTR 4880 .
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May 2021

Deep neuromuscular block does not improve surgical conditions in patients receiving sevoflurane anaesthesia for laparoscopic renal surgery.

Br J Anaesth 2021 02 20;126(2):377-385. Epub 2020 Oct 20.

Department of Anaesthesiology, Leiden University Medical Centre, Leiden, The Netherlands. Electronic address:

Background: Deep neuromuscular block is associated with improved working conditions during laparoscopic surgery when propofol is used as a general anaesthetic. However, whether deep neuromuscular block yields similar beneficial effects when anaesthesia is maintained using volatile inhalation anaesthesia has not been systematically investigated. Volatile anaesthetics, as opposed to intravenous agents, potentiate muscle relaxation, which potentially reduces the need for deep neuromuscular block to obtain optimal surgical conditions. We examined whether deep neuromuscular block improves surgical conditions over moderate neuromuscular block during sevoflurane anaesthesia.

Methods: In this single-centre, prospective, randomised, double-blind study, 98 patients scheduled for elective renal surgery were randomised to receive deep (post-tetanic count 1-2 twitches) or a moderate neuromuscular block (train-of-four 1-2 twitches). Anaesthesia was maintained with sevoflurane and titrated to bispectral index values between 40 and 50. Pneumoperitoneum pressure was maintained at 12 mm Hg. The primary outcome was the difference in surgical conditions, scored at 15 min intervals by one of eight blinded surgeons using a 5-point Leiden-Surgical Rating Scale (L-SRS) that scores the quality of the surgical field from extremely poor to optimal.

Results: Deep neuromuscular block did not improve surgical conditions compared with moderate neuromuscular block: mean (standard deviation) L-SRS 4.8 (0.3) vs 4.8 (0.4), respectively (P=0.94). Secondary outcomes, including unplanned postoperative readmissions and prolonged hospital admission, were not significantly different.

Conclusions: During sevoflurane anaesthesia, deep neuromuscular block did not improve surgical conditions over moderate neuromuscular block in normal-pressure laparoscopic renal surgery.

Clinical Trial Registration: NL7844 (
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February 2021

Reversal of Partial Neuromuscular Block and the Ventilatory Response to Hypoxia: A Randomized Controlled Trial in Healthy Volunteers.

Anesthesiology 2019 09;131(3):467-476

From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.

What We Already Know About This Topic: The ventilatory response to hypoxia is a critical reflex that is impaired by neuromuscular blocking drugs. However, the degree to which this reflex is restored after reversal of blockade is unknown.

What This Article Tells Us That Is New: Despite full reversal of neuromuscular blockade at the thumb using different drug classes, this hypoxic chemoreflex is not fully restored.

Background: The ventilatory response to hypoxia is a life-saving chemoreflex originating at the carotid bodies that is impaired by nondepolarizing neuromuscular blocking agents. This study evaluated the effect of three strategies for reversal of a partial neuromuscular block on ventilatory control in 34 healthy male volunteers on the chemoreflex. The hypothesis was that the hypoxic ventilatory response is fully restored following the return to a train-of-four ratio of 1.

Methods: In this single-center, experimental, randomized, controlled trial, ventilatory responses to 5-min hypoxia (oxygen saturation, 80 ± 2%) and ventilation at hyperoxic isohypercapnia (end-tidal carbon dioxide concentration, 55 mmHg) were obtained at baseline, during rocuronium-induced partial neuromuscular block (train-of-four ratio of 0.7 measured at the adductor pollicis muscle by electromyography), and following reversal until the train-of-four ratio reached unity with placebo (n = 12), 1 mg neostigmine/0.5 mg atropine (n = 11), or 2 mg/kg sugammadex (n = 11).

Results: This study confirmed that low-dose rocuronium reduced the ventilatory response to hypoxia from 0.55 ± 0.22 (baseline) to 0.31 ± 0.21 l · min · % (train-of-four ratio, 0.7; P < 0.001). Following full reversal as measured at the thumb, there was persistent residual blunting of the hypoxic ventilatory response (0.45 ± 0.16 l · min · %; train-of-four ratio, 1.0; P < 0.001). Treatment effect was not significant (analysis of covariance, P = 0.299) with chemoreflex impairment in 5 (45%) subjects following sugammadex reversal, in 7 subjects (64%) following neostigmine reversal, and in 10 subjects (83%) after spontaneous reversal to a train-of-four ratio of 1.

Conclusions: Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at train-of-four ratios greater than 0.9 following reversal with neostigmine and sugammadex or spontaneous recovery of the neuromuscular block.
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September 2019

Effects of Thoracic Epidural Anesthesia on Neuronal Cardiac Regulation and Cardiac Function.

Anesthesiology 2019 03;130(3):472-491

From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (J.W., B.T.V., L.P.H.J.A.) Department of Anesthesia and Perioperative Medicine, Ghent University, Ghent, Belgium (P.F.W.).

Cardiac sympathetic blockade with high-thoracic epidural anesthesia is considered beneficial in patients undergoing major surgery because it offers protection in ischemic heart disease. Major outcome studies have failed to confirm such a benefit, however. In fact, there is growing concern about potential harm associated with the use of thoracic epidural anesthesia in high-risk patients, although underlying mechanisms have not been identified. Since the latest review on this subject, a number of clinical and experimental studies have provided new information on the complex interaction between thoracic epidural anesthesia-induced sympatholysis and cardiovascular control mechanisms. Perhaps these new insights may help identify conditions in which benefits of thoracic epidural anesthesia may not outweigh potential risks. For example, cardiac sympathectomy with high-thoracic epidural anesthesia decreases right ventricular function and attenuates its capacity to cope with increased right ventricular afterload. Although the clinical significance of this pathophysiologic interaction is unknown at present, it identifies a subgroup of patients with established or pending pulmonary hypertension for whom outcome studies are needed. Other new areas of interest include the impact of thoracic epidural anesthesia-induced sympatholysis on cardiovascular control in conditions associated with increased sympathetic tone, surgical stress, and hemodynamic disruption. It was considered appropriate to collect and analyze all recent scientific information on this subject to provide a comprehensive update on the cardiovascular effects of high-thoracic epidural anesthesia and cardiac sympathectomy in healthy and diseased patients.This review provides a comprehensive update on the cardiovascular effects of high-thoracic epidural anesthesia and cardiac sympathectomy in healthy and diseased patients.
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March 2019

The use of surgical rating scales for the evaluation of surgical working conditions during laparoscopic surgery: a scoping review.

Surg Endosc 2019 01 14;33(1):19-25. Epub 2018 Sep 14.

Department of Anesthesiology, Leiden University Medical Center, Albinusdreef 2, 2333, Leiden, The Netherlands.

Introduction: Surgical rating scales (SRSs) enable the surgeon to uniformly quantify surgical working conditions. They are increasingly used as a primary outcome in studies evaluating the effect of anaesthesia or surgery-related interventions on the quality of the surgical work field. SRSs are especially used in laparoscopic surgery due to a renewed interest in deep neuromuscular block. There are however no guidelines regarding the uniform use of SRS and the uniform reporting of results.

Methods: A systematic search was conducted in the databases of PubMed, Web of Science and Embase for studies that reported the use of an SRS to evaluate surgical conditions in laparoscopic surgery. Only original human research in English language with full text availability through the Leiden university library was considered for this review. The full texts of eligible abstracts were independently reviewed by the first and second author. The quality of SRSs and methodology of rating were systematically reviewed.

Results: The search yielded 2830 reports, of which 17 were identified using a surgical rating scale (SRS) in laparoscopic surgery. Ten of these reports used a unique SRS, these were systematically appraised for their quality. The overall quality of the SRSs was low: the majority of the scales were poorly described and lacked assessment of inter- and intra-rater reliability. In addition, considerable differences exist in the methodology of rating and the reporting of results.

Conclusion: There is substantial inconsistency in SRS quality, methodology, and results reporting. The uniform use of high-quality surgical rating scales is needed to improve the quality and reproducibility of future research.
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January 2019

Vasoplegia After Surgical Left Ventricular Restoration: 2-Year Follow-Up.

Ann Thorac Surg 2018 11 14;106(5):1371-1378. Epub 2018 Aug 14.

Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:

Background: Vasoplegia is a severe complication that can develop after surgical procedures for heart failure. The current study evaluated the effect of vasoplegia on survival, cardiac function, and renal function 2 years after surgical left ventricular restoration (SVR).

Methods: Heart failure patients with a left ventricular ejection fraction (LVEF) of 0.35 or less who underwent SVR in 2006 to 2014 were included. Vasoplegia was defined as the continuous need of vasopressors (norepinephrine ≥0.2 μg · kg · min or terlipressin [any dose], or both) combined with a cardiac index of 2.2 L · min · m or higher for at least 12 consecutive hours, starting within the first 3 days postoperatively. The effect of vasoplegia on mortality, New York Heart Association Functional Classification, LVEF, and creatinine clearance was assessed up to 2 years of follow-up.

Results: SVR was performed in 113 patients (80% men), aged 62 ± 10 years, and with an LVEF of 0.25 ± 0.06. Postoperative vasoplegia developed in 23%. Survival was lower in patients with vasoplegia compared with patients without vasoplegia at 6 months (62% vs 90%, p = 0.001) and at 2 years (50% versus 84%, p < 0.001). At the 2-year follow-up, New York Heart Association class and LVEF had improved and were similar in both groups (respectively, p = 0.319 and p = 0.444). Creatinine clearance was lower in patients with vasoplegia compared with patients without vasoplegia 2 years postoperatively (p < 0.001), even after correcting for baseline creatinine clearance (p = 0.009).

Conclusions: Vasoplegia after SVR is associated with decreased survival. Despite an improved and similar cardiac function, renal function was compromised in vasoplegic patients at the 2-year follow-up.
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November 2018

Electronic Nose Technology Fails to Sniff Out Acute Mountain Sickness.

High Alt Med Biol 2018 Sep 20;19(3):232-236. Epub 2018 Mar 20.

4 Institute of Sport Sciences, University of Lausanne , Lausanne, Switzerland .

Berendsen, Remco R., Marieke E. van Vessem, Marcel Bruins, Luc J.S.M. Teppema, Leon P.H.J. Aarts, and Bengt Kayser. Electronic nose technology fails to sniff out acute mountain sickness. High Alt Med Biol. 19:232-236, 2018.

Aim: The aim of the study was to evaluate whether an electronic nose can discriminate between individuals with and without acute mountain sickness (AMS) following rapid ascent to 4554 m.

Results: We recruited recreational climbers (19 women, 82 men; age 35 ± 10 years, mean ± standard deviation [SD]) upon arrival at 4554 m (Capanna Regina Margherita, Italy) for a proof of concept study. AMS was assessed with the Lake Louise self-report score (LLSRS) and the abbreviated Environmental Symptoms Questionnaire (ESQc); scores ≥3 and ≥0.7 were considered AMS, respectively. Exhaled air was analyzed with an electronic nose (Aeonose; The eNose Company, Netherlands). The collected data were analyzed using an artificial neural network. AMS prevalence was 44% with the LLSRS (mean score of those sick 4.4 ± 1.4 [SD]) and 20% with the ESQc (1.2 ± 0.5). The electronic nose could not discriminate between AMS and no AMS (LLSRS p = 0.291; ESQc p = 0.805).

Conclusion: The electronic nose technology utilized in this study could not discriminate between climbers with and without symptoms of AMS in the setting of an acute exposure to an altitude of 4554 m. At this stage, we cannot fully exclude that this technology per se is not able to discriminate for AMS. The quest for objective means to diagnose AMS thus continues.
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September 2018

Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain.

Invest Ophthalmol Vis Sci 2017 05;58(6):BIO52-BIO60

Araim Pharmaceuticals, Tarrytown, New York, United States.

Purpose: Sarcoidosis frequently is complicated by small nerve fiber loss (SNFL), which can be quantified using corneal confocal microscopy (CCM). Prior studies suggest that the innate repair receptor agonist cibinetide reverses corneal nerve loss. This phase 2b, 28-day, randomized trial of 64 subjects with sarcoid-associated SNFL and neuropathic pain assessed the effect of cibinetide on corneal nerve fiber area (CNFA) and regenerating intraepidermal fibers (GAP-43+) as surrogate endpoints for disease modification, pain severity, and functional capacity (6-minute walk test [6MWT]).

Methods: Cibinetide (1, 4, or 8 mg/day) was compared to placebo. The primary study endpoint was a change in CNFA at 28 days.

Results: The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively. Intraepidermal GAP-43+ fibers increased in the 4 mg group (P = 0.035). Further, changes in CNFA correlated with changes in GAP-43+ (ρ = 0.575; P = 0.025) and 6MWT (ρ = 0.645; P = 0.009). Pain improved significantly in all groups, with subjects having moderate-severe pain reporting a clinically meaningful placebo-corrected decrease in pain intensity in the 4 mg group (P = 0.157).

Conclusions: Cibinetide significantly increased small nerve fiber abundance in the cornea and skin, consistent with a disease modifying effect. The relationships between CNFA and other clinical measures of disease support its use as a surrogate endpoint to assess potential disease modifying therapies for neuropathy.
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May 2017

Deep Neuromuscular Block and Surgical Conditions During Bariatric Surgery.

Anesth Analg 2017 06;124(6):2094-2095

Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands,

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June 2017

Thoracic Epidural Anesthesia Reduces Right Ventricular Systolic Function With Maintained Ventricular-Pulmonary Coupling.

Circulation 2016 10 14;134(16):1163-1175. Epub 2016 Sep 14.

From the Department of Anesthesiology (J.W., E.L.A.v.D., B.T.V., L.P.H.J.A.), Department of Intensive Care (R.B.P.d.W.), Department of Cardiothoracic Surgery (M.I.M.V.), and Department of Cardiology (P.S.), Leiden University Medical Center, The Netherlands; and the Department of Anesthesia, University Hospitals Ghent, Belgium (P.F.W.).

Background: Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling.

Methods: In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters.

Results: Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV: +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dt, and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV: -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia.

Conclusions: Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia.

Clinical Trial Registration: URL: Unique identifier: NTR2844.
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October 2016

Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women.

Exp Physiol 2016 Sep;101(9):1230-1240

Leiden University Medical Center, Department of Anesthesiology, Leiden, The Netherlands.

New Findings: What is the central question of this study? Does a clinically relevant intravenous dose of erythropoeitin affect the hypoxic ventilatory response and/or hypoxic pulmonary vasoconstriction in healthy humans? What is the main finding and its importance? Erythropoeitin does not influence the ventilatory and pulmonary vascular responses to acute hypoxia in men or women. Sustained and chronic hypoxia lead to an increase in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical i.v. dose of recombinant human erythropoietin (50 IU kg ) on the isocapnic HVR and HPV in seven male and seven female subjects by exposing them to hypoxia for 20 min (end-tidal  ∼50 mmHg) while measuring their ventilation and estimating pulmonary arterial pressure from the maximal velocity of the regurgitant jet over the tricuspid valve during systole (ΔP ) with echocardiography. In the placebo session, after 5 and 20 min men responded with an increase in ventilation by 0.0056 and 0.0023 l min  kg   , respectively, indicating the presence of hypoxic ventilatory depression. In women, the increase in ventilation was 0.0067 and 0.0047 l min  kg   , respectively. In both sexes, erythropoietin did not alter these responses significantly. In the placebo session, mean ΔP increased by 6.1 ± 0.7 mmHg in men (P = 0.035) and by 8.4 ± 1.4 mmHg in women (P = 0.020) during the hypoxic exposure, whereby women had a ∼5 mmHg lower end-tidal . Erythropoietin did not alter these responses; in men, ΔP increased by 7.5 ± 1.1 mmHg (n.s. versus placebo) and in women by 9.7 ± 2.2 mmHg (n.s. versus placebo). We conclude that women tended to have a greater HPV in placebo conditions and that a clinical dose of erythropoietin has no effect on the HVR and HPV in either sex.
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September 2016

Effect of increasing age on the haemodynamic response to thoracic epidural anaesthesia: an observational study.

Eur J Anaesthesiol 2014 Nov;31(11):597-605

From the Department of Anaesthesiology, Leiden University Medical Centre, Leiden, the Netherlands (JW, BTV, PHJA), and Department of Anaesthesia, University Hospitals Ghent, Ghent, Belgium (PFW).

Background: Sympathetic blockade with thoracic epidural anaesthesia (TEA) results in circulatory changes and may directly alter cardiac function. Ageing is associated with an impairment of autonomic nervous system control and a deterioration of myocardial diastolic performance.

Objectives: We postulated that haemodynamic changes induced by TEA could vary with age.

Design: An observational study.

Settings: Tertiary, university hospital.

Patients: Thirty-five patients scheduled for pulmonary surgery and TEA stratified into three age groups: 18 to 45 years; 46 to 65 years; and at least 66 years.

Interventions: Cardiac performance was evaluated in awake patients using transthoracic echocardiography (TTE) at baseline and 45 min after institution of TEA. Intravenous volume loading was used to preserve preload.

Main Outcome Measures: Tissue Doppler imaging (TDI) and other derived indices from TTE were used to quantify biventricular systolic and diastolic function.

Results: Baseline systolic and diastolic left ventricular function and right ventricular diastolic function decreased with age. After TEA, mean arterial pressure (MAP) decreased (91.2 vs. 79.2 mmHg; P < 0.001) and cardiac index increased (2.7 vs. 3.0 l min m; P = 0.005), although heart rate and Doppler-derived indices of left ventricular contractility remained unchanged. Right ventricular ejection indices increased and TDI-derived measures of diastolic performance increased for the left ventricle (LV) as well as the right ventricle (RV). With the exception of Tricuspid Annular Plane Systolic Excursion (TAPSE), which increased with increasing age (R = 0.53; P = 0.003), TEA effects on biventricular function were not influenced by age.

Conclusion: When preload is preserved with volume loading, TEA predominantly causes systemic vasodilatation and increases global haemodynamic performance. Indices of left ventricular systolic function do not change, whereas left ventricular and right ventricular diastolic function appears to improve. The effects of TEA on right ventricular systolic function are inconclusive. Although increasing age causes a consistent decline of baseline diastolic function, the cardiovascular response to TEA is not impaired in the elderly.

Trial Registry Number: EudraCT 2009-010594-20.
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November 2014

Defining fluid responsiveness: a guide to patient-tailored volume titration.

J Cardiothorac Vasc Anesth 2014 Jun;28(3):745-54

Department of Intensive Care Medicine, Academic Medical Centre, Amsterdam, the Netherlands.

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June 2014

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

Brain Connect 2014 Aug;4(6):404-16

1 Department of Anesthesiology, Leiden University Medical Center , Leiden, The Netherlands .

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.
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August 2014

Minimised closed circuit coronary artery bypass grafting in the elderly is associated with lower levels of organ-specific biomarkers: a prospective randomised study.

Eur J Anaesthesiol 2013 Nov;30(11):685-94

From the Department of Cardio-Thoracic Surgery, Leiden University Medical Centre, Leiden (W-JPvB, RJK), Department of Clinical Chemistry and Haematological Laboratory, Gelre Hospital, Apeldoorn (WBG), Department of Cardio-Thoracic Surgery, Academic Medical Centre Amsterdam, Amsterdam (AHD), Department of Anaesthesiology, Intensive Care and Pain Management, St Antonius Hospital, Nieuwegein (EPvD), Department of Anaesthesiology Leiden University Medical Centre, Leiden (LPA), The Netherlands.

Background: Restrictive fluid management may protect organ function and improve postoperative outcome in elderly coronary artery bypass grafting (CABG) patients.

Objective: We assessed organ-specific biomarker release to study the contribution of a fluid restrictive closed circuit concept to organ protection in elderly CABG patients. Cardiac, respiratory and abdominal organ injury was measured during and following minimal fluid coronary artery bypass grafting (mCABG), off-pump coronary artery bypass (opCAB) surgery and conventional CABG with high volume prime and cold crystalloid cardioplegia (cCABG). The results were related to differences in clinical outcome.

Design: Prospective randomised trial.

Setting: Dutch tertiary single centre study.

Patients: Sixty patients over 70 years of age (38 men and 22 women) were randomised to one of the three different techniques. Inclusion criteria were as follows: first time CABG, elective surgery, ejection fraction more than 30% and multivessel disease. Acetylsalicylic acid and clopidogrel administration or requiring less than three distal anastomoses were an exclusion.

Main Outcome Measures: Organ-specific markers of the heart--heart fatty acid binding protein (HFABP), troponin T, pro-brain natriuretic peptide (pro-BNP) and creatinine phosphokinase (CPK), lung clara cell 16 protein, pneumoprotein (CC16), intestinal fatty acid binding protein (IFABP) and liver glutathione S-transferase (α-GST)--were measured perioperatively. Postoperative PaO2 levels, ventilation time, blood product consumption and adverse events were noted.

Results: Myocardial organ-specific biomarker troponin T showed significantly lower median levels during mCABG compared with the cCABG and opCAB groups [troponin 0.25 mg l(-1) (interquartile range, IQR 0.18 to 0.40), 0.39 mg l(-1) (IQR 0.23 to 0.49) and 0.36 mg l(-1) (IQR 0.23 to 0.50), respectively (P<0.003)]. HFABP, IFABP and α-GST levels were significantly higher during cCABG compared with opCAB and mCABG [HFABP 38.6 mg l(-1) (IQR 29.6 to 47.1), 23.3 mg l(-1) (IQR 16.5 to 31.0) and 21.1 mg l(-1) (IQR 15.7 to 28.8; P<0.001), IFABP 0.57 mg l(-1) (IQR 0.37 to 1.11), 0.44 mg l(-1) (IQR 0.16 to 0.74) and 0.37 mg l(-1) (IQR 0.13 to 1.05; P<0.02) and α-GST 11.5 mg l(-1) (IQR 7.7 to 15.7), 7.0 mg l(-1) (IQR 4.5 to 13.8) and 7.3 mg l(-1) (IQR 6.2 to 11.2), respectively (P<0.009)]. There was a trend towards higher median CC16 levels in the cCABG group (P<0.07). CPK and pro-BNP were not significantly different. On the first postoperative day, PaO2 levels and duration of mechanical ventilation were significantly improved, and there was lower use of blood products in the mCABG group than in the cCABG and opCAB groups (P<0.05).

Conclusion: Following mCABG with low volume myocardial preservation and restrictive fluid management, early respiratory performance was improved and consumption of blood products reduced compared with opCAB and cCABG.
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November 2013

Impact of different surgical strategies on perioperative protein S100β release in elderly patients undergoing coronary artery bypass grafting.

Innovations (Phila) 2013 May-Jun;8(3):230-6

Department of Cardio Thoracic Surgery, Leiden University Medical Centre, Leiden, The Netherlands.

Objective: This study was designed to compare neurological injury-associated protein S100β release during three different treatment modalities, minimized closed circuit coronary artery bypass grafting (CABG) (MCABG), off-pump CABG (OPCAB), and conventional CABG (CCABG), comprising high-volume prime and cold crystalloid cardioplegia. Our working hypothesis was that fluid restriction as provided by MCABG may decrease neurological injury-associated protein S100β release.

Methods: In this prospective trial, in a tertiary center, 30 surgical patients (aged >70 years, 25 men and 5 women) undergoing first-time elective CABG were enrolled. The inclusion criteria were three-vessel disease and elective surgery. The exclusion criteria were left ventricular ejection fraction of less than 30%, use of clopidogrel, carotid disease, or needing fewer than three distal anastomoses. Protein S100β concentrations, hematocrit (Ht) levels, and PO2 levels were measured after induction of anesthesia, 10 minutes after reperfusion, upon arrival at the intensive care unit, 3 hours postoperatively at the intensive care unit, and the next morning. Statistics consisted of areas under the curve, peak levels, and correlation and variance tests.

Results: A significant negative correlation was found indicating higher S100β release at lower Ht levels and at lower PO2 levels in all study groups. The lowest S100β variance was measured during MCABG (Wilks Λ P = 0.052). The perioperative Ht was significantly higher in the MCABG group and in the OPCAB group compared with the CCABG group (P = 0.04 vs P < 0.01). At all time points, the S100β protein concentration showed no significant differences between the different surgical techniques. The mean (95% confidence interval) values of S100 area under the curve were the following: CCABG, 2.3 (1.06-3.5); MCABG, 1.44 (0.6-2.21); and OPCAB, 1.87 (1.5-2.19) [independent nonparametric Kruskal-Wallis test (P = 0.13)]. The mean (95% confidence interval) peak S100 values (calculated as the maximum value seen in a patient during the research period) were the following: CCABG, 1.07 (0.4-1.68); MCABG, 0.59 (0.28-0.90); and OPCAB, 0.83 (0.59-1.06) [independent nonparametric Kruskal-Wallis test (P = 0.22)].

Conclusions: Despite similar perioperative S100β protein release for all techniques studied, higher Ht and PO2 levels correlated with lower S100β release within all study groups. The low S100β variance during the fluid restrictive MCABG technique may be due to more efficient oxygen transport to the brain provided by significantly higher perioperative Ht levels. Further prospective data are required to better understand this complex issue.
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April 2014

Effect of variations in depth of neuromuscular blockade on rating of surgical conditions by surgeon and anesthesiologist in patients undergoing laparoscopic renal or prostatic surgery (BLISS trial): study protocol for a randomized controlled trial.

Trials 2013 Mar 1;14:63. Epub 2013 Mar 1.

Department of Anesthesiology, Leiden University Medical Center, P5-Q, RC Leiden, 2330, The Netherlands.

Background: Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation. Especially in procedures that are confined to a narrow working field, such as retroperitoneal laparoscopic surgery, deep neuromuscular relaxation may be beneficial. Until recently, though, deep neuromuscular block (NMB) came at the expense of a variety of issues that conflicted with its use. However, with the introduction of sugammadex, rapid reversal of a deep NMB is feasible. In the current protocol, the association between the depth of NMB and rating of surgical conditions by the surgeon and anesthesiologist is studied.

Methods/design: This is a single-center, prospective, randomized, blinded, parallel group and controlled trial. Eligible patients are randomly assigned to one of two groups: (1) deep NMB (post-tetanic count, one or two twitches; n = 12) and (2) moderate NMB (train-of-four, 1 to 2 twitches, n = 12) by administration of high-dose rocuronium in Group 1 and a combination of atracurium and mivacurium in Group 2. The NMB in Group 1 is reversed by 4 mg/kg sugammadex; the NMB in Group 2 by 1 mg neostigmine and 0.5 mg atropine. Patients are eligible if they are over 18 years, willing to sign the informed consent form, and are scheduled to undergo an elective laparoscopic renal procedure or laparoscopic prostatectomy. A single surgeon performs the surgeries and rates the surgical conditions on a five-point surgical rating scale (SRS) ranging from 1 (poor surgical conditions) to 5 (excellent surgical conditions). The intra-abdominal part of the surgeries is captured on video and a group of five anesthesiologists and ten surgical experts will rate the videos using the same SRS. The primary analysis will be an intention-to-treat analysis. Evaluation will include the association between the level of NMB and SRS, as obtained by the surgeon performing the procedure and the agreement between the scoring of the images by anesthesiologists and surgeons.

Discussion: We aim to show that under the right conditions the perceived opposing goals of surgeons and anesthesiologists (optimal surgical conditions vs. optimal postoperative conditions) may be met without compromise to either.

Trial Registration: identifier NCT01631149.
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March 2013

Comprehensive review: is it better to use the Trendelenburg position or passive leg raising for the initial treatment of hypovolemia?

J Clin Anesth 2012 Dec;24(8):668-74

Department of Anesthesiology, Leiden University Medical Centre, 2300 RC Leiden, the Netherlands.

Hypovolemia is a common clinical problem. The Trendelenburg position and passive leg raising (PLR) are routinely used in the initial treatment while awaiting fluid resuscitation. In this meta-analysis, we evaluated the hemodynamic effects of PLR and Trendelenburg positioning to determine which position had the most optimal effect on cardiac output (CO). Databases were searched for prospective studies published between 1960 and 2010 in normovolemic or hypovolemic humans; these studies had to investigate the hemodynamic effects within 10 minutes of a postural change from supine. Twenty-one studies were included for PLR (n=431) and 13 studies for Trendelenburg position (n=246). Trendelenburg position increased mean arterial pressure (MAP). Cardiac output increased 9%, or 0.35 L/min, at one minute of head-down tilt. Between 2 and 10 minutes, this increase in CO decreased to 4%, or 0.14 L/min, from baseline. Cardiac output increased at one minute of leg elevation by 6%, or 0.19 L/min. The effect persisted after this period by 6%, or 0.17 L/min. Both Trendelenburg and PLR significantly increased CO, but only PLR seemed to sustain this effect after one minute. Although the Trendelenberg position is a common maneuver for nurses and doctors, PLR may be the better intervention in the initial treatment of hypovolemia.
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December 2012

Bedside assessment of total systemic vascular compliance, stressed volume, and cardiac function curves in intensive care unit patients.

Anesth Analg 2012 Oct 4;115(4):880-7. Epub 2012 Jul 4.

Department of Intensive Care, Leiden University Medical Center, Leiden, The Netherlands.

Background: Mean systemic filling pressure (Pmsf) can be measured at the bedside with minimally invasive monitoring in ventilator-dependent patients using inspiratory hold maneuvers (Pmsf(hold)) as the zero flow intercept of cardiac output (CO) to central venous pressure (CVP) relation. We compared Pmsf(hold) with arm vascular equilibrium pressure during vascular occlusion (Pmsf(arm)) and their ability to assess systemic vascular compliance (Csys) and stressed volume by intravascular fluid administration.

Methods: In mechanically ventilated postoperative cardiac surgery patients, inspiratory holds at varying airway pressures and arm stop-flow maneuvers were performed during normovolemia and after each of 10 sequential 50-mL bolus colloid infusions. We measured CVP, Pmsf(arm), stroke volume, and CO during fluid administration steps to construct CVP to CO (cardiac function) curves and Δvolume/ΔPmsf (compliance) curves. Pmsf(hold) was measured before and after fluid administration. Stressed volume was determined by extrapolating the Pmsf-volume curve to zero pressure intercept.

Results: Fifteen patients were included. Pmsf(hold) and Pmsf(arm) were closely correlated. Csys was linear (64.3 ± 32.7 mL · mm Hg(-1), 0.97 ± 0.49 mL · mm Hg(-1) · kg(-1) predicted body weight). Stressed volume was estimated to be 1265 ± 541 mL (28.5% ± 15% predicted total blood volume). Cardiac function curves of patients with an increase of >12% to 500 mL volume extension (volume responsive) were steep, whereas the cardiac function curves of the remaining patients were flat.

Conclusions: Csys, stressed volume, and cardiac function curves can be determined at the bedside and can be used to characterize patients' hemodynamic status.
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October 2012

Hypertensive crisis during adrenalectomy in a patient with pheochromocytoma and a HOCM with SAM.

Hormones (Athens) 2013 Jul-Sep;12(3):472-4

Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.

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April 2014

Determination of vascular waterfall phenomenon by bedside measurement of mean systemic filling pressure and critical closing pressure in the intensive care unit.

Anesth Analg 2012 Apr 17;114(4):803-10. Epub 2012 Feb 17.

Department of Intensive Care, B4, Leiden University Medical Center, P.O.B. 9600, 2300 RC Leiden, The Netherlands.

Background: Mean systemic filling pressure (Pmsf) can be determined at the bedside by measuring central venous pressure (Pcv) and cardiac output (CO) during inspiratory hold maneuvers. Critical closing pressure (Pcc) can be determined using the same method measuring arterial pressure (Pa) and CO. If Pcc > Pmsf, there is then a vascular waterfall. In this study, we assessed the existence of a waterfall and its implications for the calculation of vascular resistances by determining Pmsf and Pcc at the bedside.

Methods: In 10 mechanically ventilated postcardiac surgery patients, inspiratory hold maneuvers were performed, transiently increasing Pcv and decreasing Pa and CO to 4 different steady-state levels. For each patient, values of Pcv and CO were plotted in a venous return curve to determine Pmsf. Similarly, Pcc was determined with a ventricular output curve plotted for Pa and CO. Measurements were performed in each patient before and after volume expansion with 0.5 L colloid, and vascular resistances were calculated.

Results: For every patient, the relationship between the 4 measurements of Pcv and CO and of Pa and CO was linear. Baseline Pmsf was 18.7 ± 4.0 mm Hg (mean ± SD) and differed significantly from Pcc 45.5 ± 11.1 mm Hg (P < 0.0001). The difference of Pcc and Pmsf was 26.8 ± 10.7 mm Hg, indicating the presence of a systemic vascular waterfall. Volume expansion increased Pmsf (26.3 ± 3.2 mm Hg), Pcc (51.5 ± 9.0 mm Hg), and CO (5.5 ± 1.8 to 6.8 ± 1.8 L · min(-1)). Arterial (upstream of Pcc) and venous (downstream of Pmsf) vascular resistance were 8.27 ± 4.45 and 2.75 ± 1.23 mm Hg · min · L(-1); the sum of both (11.01 mm Hg · min · L(-1)) was significantly different from total systemic vascular resistance (16.56 ± 8.57 mm Hg · min · L(-1); P = 0.005). Arterial resistance was related to total resistance.

Conclusions: Vascular pressure gradients in cardiac surgery patients suggest the presence of a vascular waterfall phenomenon, which is not affected by CO. Thus, measures of total systemic vascular resistance may become irrelevant in assessing systemic vasomotor tone.
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April 2012

Arm occlusion pressure is a useful predictor of an increase in cardiac output after fluid loading following cardiac surgery.

Eur J Anaesthesiol 2011 Nov;28(11):802-6

Department of Anaesthesiology, Leiden University Medical Centre, P-05, Albinusdreef 2, PO Box 9600, 2500 RC Leiden, The Netherlands.

Background And Objective: In pharmacological research, arm occlusion pressure is used to study haemodynamic effects of drugs. However, arm occlusion pressure might be an indicator of static filling pressure of the arm. We hypothesised that arm occlusion pressure can be used to predict fluid loading responsiveness.

Methods: Twenty-four patients who underwent cardiac surgery were studied during their first 2 h in the ICU. The lungs were ventilated mechanically and left ventricular function was supported as necessary. Arm occlusion pressure was defined as the radial artery pressure after occluding arterial flow for 35 s by a blood pressure cuff inflated to 50 mmHg above SBP. The cuff was positioned around the arm in which a radial artery catheter had been inserted. Measurements were performed before (baseline) and after fluid loading (500 ml hydroxyethyl starch 6%). Patients whose cardiac output increased by at least 10% were defined as responders.

Results: In responders (n = 17), arm occlusion pressure, mean arterial pressure and central venous pressure increased and stroke volume variation and pulse pressure variation decreased. In non-responders (n = 7), arm occlusion pressure and central venous pressure increased, and pulse pressure variation decreased. Mean arterial pressure, stroke volume variation and heart rate did not change significantly. The area under the curve to predict fluid loading responsiveness for arm occlusion pressure was 0.786 (95% confidence interval 0.567-1.000), at a cut-off of 21.9 mmHg, with sensitivity of 71% and specificity of 88% in predicting fluid loading responsiveness. Prediction of responders with baseline arm occlusion pressure was as good as baseline stroke volume variation and pulse pressure variation.

Conclusion: Arm occlusion pressure was a good predictor of fluid loading responsiveness in our group of cardiac surgery patients and offers clinical advantages over stroke volume variation and pulse pressure variation.
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November 2011

Hemorrhagic shock-induced endothelial cell activation in a spontaneous breathing and a mechanical ventilation hemorrhagic shock model is induced by a proinflammatory response and not by hypoxia.

Anesthesiology 2011 Sep;115(3):474-82

Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Introduction: The interaction between neutrophils and activated endothelium is essential for the development of multiple organ dysfunction in patients with hemorrhagic shock (HS). Mechanical ventilation frequently is used in patients with HS. The authors sought to investigate the consequences of mechanical ventilation of mice subjected to HS on microvascular endothelial activation in the lung and kidney.

Methods: Anesthetized wild type C57BL/6 male mice were subjected to controlled hemorrhage; subgroups of mice were mechanically ventilated during the HS insult. To study the effect of acute hypoxia on the mice, the animals were housed in hypoxic cages. Gene expression levels was assessed by quantitative real-time polymerase chain reaction. Protein expression was assessed by immunohistochemistry and enzyme-linked immunosorbent assay.

Results: Ninety minutes after the shock induction, a vascular bed-specific, heterogeneous proinflammatory endothelial activation represented by E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 expression was seen in kidney and lung. No differences in adhesion molecules between the spontaneously breathing and mechanically ventilated mice were found. Concentrations of the proinflammatory cytokines chemokine (C-X-C motif) ligand 1 (11.0-fold) and interleukin-6 (21.7-fold) were increased after 90 min of HS. Two hours of 6% oxygen did not induce the expression of E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 in the kidneys and the lung.

Conclusions: Hemorrhagic shock leads to an early and reversible proinflammatory endothelial activation in kidney and lung. HS-induced endothelial activation is not changed by mechanical ventilation during the shock phase. Hypoxia alone does not lead to endothelial activation. The observed proinflammatory endothelial activation is mostly ischemia- or reperfusion-dependent and not related to hypoxia.
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September 2011

Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: a report of 3 cases.

Pain 2011 Sep 4;152(9):2173-2178. Epub 2011 May 4.

Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg Hospital, Aarhus University Hospital, 9000 Aalborg, Denmark.

Studies on the efficacy of ketamine in the treatment of chronic pain indicate that prolonged or repetitive infusions are required to ensure prolonged pain relief. Few studies address ketamine-induced toxicity. Here we present data on the occurrence of ketamine-induced liver injury during repeated administrations of S(+)-ketamine for treatment of chronic pain in patients with complex regional pain syndrome type 1 as part of a larger study exploring possible time frames for ketamine re-administration. Six patients were scheduled to receive 2 continuous intravenous 100-hour S(+)-ketamine infusions (infusion rate 10-20mg/h) separated by 16 days. Three of these patients developed hepatotoxicity. Patient A, a 65-year-old woman, developed an itching rash and fever during her second exposure. Blood tests revealed elevated liver enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and γ-glutamyl transferase, all ≥ 3 times the upper limit of normal) and modestly increased eosinophilic leukocytes. Patient E, a 48-year-old woman, developed elevated liver enzymes of similar pattern as Patient A during her second ketamine administration and a weakly positive response to antinuclear antibodies. In a third patient, Patient F, a 46-year-old man, elevated liver enzymes (alanine transaminase and γ-glutamyl transferase) were detected on the first day of his second exposure. In all patients, the ketamine infusion was promptly terminated and the liver enzymes slowly returned to reference values within 2 months. Our data suggest an increased risk for development of ketamine-induced liver injury when the infusion is prolonged and/or repeated within a short time frame. Regular measurements of liver function are therefore required during such treatments.
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September 2011

Methods in pharmacology: measurement of cardiac output.

Br J Clin Pharmacol 2011 Mar;71(3):316-30

Departments of Anaesthesiology Intensive Care Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Many methods of cardiac output measurement have been developed, but the number of methods useful for human pharmacological studies is limited. The 'holy grail' for the measurement of cardiac output would be a method that is accurate, precise, operator independent, fast responding, non-invasive, continuous, easy to use, cheap and safe. This method does not exist today. In this review on cardiac output methods used in pharmacology, the Fick principle, indicator dilution techniques, arterial pulse contour analysis, ultrasound and bio-impedance are reviewed.
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March 2011

Partitioning the resistances along the vascular tree: effects of dobutamine and hypovolemia in piglets with an intact circulation.

J Clin Monit Comput 2010 Oct 28;24(5):377-84. Epub 2010 Aug 28.

Department of Anesthesiology, Leiden University Medical Center, P-05, Albinusdreef 2, P.O. box 9600, 2300 RC, Leiden, The Netherlands.

Objective: We present a new physiological model that discriminated between changes in the systemic arterial and venous circulation. To test our model, we studied the effects of dobutamine and hypovolemia in intact pentabarbital-anesthetized piglets.

Methods: Aorta pressure (Pao), central venous pressure (Pcv), mean systemic filling pressure (Pmsf) and cardiac output (CO), were measured in 10 piglets, before, during and after dobutamine infusion (6 µg kg⁻¹ min⁻¹), as well as during hypovolemia (-10 mL kg⁻¹), and after fluid resuscitation to normovolemia. Venous (Rv) and total systemic (Rsys) resistance were determined from Pao, Pcv, Pmsf and CO. The quotient of Rv/Rsys was used to determine the predominant location of vascular changes (i.e. vasoconstriction or dilatation on either venous or arterial side).

Results: Administration of dobutamine increased heart rate and CO, whereas it decreased Pmsf, Rsys, Rv and Rv/Rsys. The decrease in Rv was significantly greater than Rsys. Pao and Pcv did not change. Hypovolemia decreased CO, Pcv, Pmsf, Rv and Rv/Rsys, but kept Rsys constant and increased heart rate.

Conclusions: Hypovolemia and dobutamine differentially alter Pmsf, Rsys, Rv and Rv/Rsys ratio. The increase in CO during dobutamine infusion was attributed to the combined increased cardiac function and decreased Rv. The decrease in CO with hypovolemia was due to a decreased Pmsf but was partly compensated for by a decrease in Rv tending to preserve venous return and thus CO.
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October 2010

Implementation of Boussignac continuous positive airway pressure in the coronary care unit: experiences and attitudes.

Heart Lung 2008 Nov-Dec;37(6):449-54

Thoraxcenter, Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.

Objective: Boussignac continuous positive airway pressure (BCPAP) delivered by face mask is useful for patients with acute cardiogenic pulmonary edema (ACPE). Although BCPAP is medically effective, we observed that not all suitable patients received it. In this descriptive, prospective, cohort study, we explored the experiences and attitudes of both patients and staff with BCPAP.

Methods: Patients were interviewed 12 to 48 hours after treatment with BCPAP. Nurses on the coronary care unit were interviewed on their knowledge, skills, experiences, and opinions concerning BCPAP.

Results: Of 117 patients with ACPE, 87 patients (74%) received BCPAP treatment. It was decided not to administer BCPAP in 30 patients with ACPE (26%). Patients who received BCPAP found that the reduction of dyspnea outweighed any discomfort. Barriers for the use of BCPAP were not related to nurses' skills but to the following: the nurses' belief that BCPAP created major discomfort, the lack of guidelines, the ultimate improvement of oxygenation without BCPAP, and the more labor-intensive treatment.

Conclusion: Overestimation of patient discomfort by nurses and system-related factors impeded the use of BCPAP for all patients with ACPE.
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February 2009

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

Eur J Cardiothorac Surg 2008 Nov 27;34(5):969-75. Epub 2008 Sep 27.

Department of Cardiothoracic Surgery, Sint Antonius Hospital, Nieuwegein, The Netherlands.

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.
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November 2008

Boussignac continuous positive airway pressure for the management of acute cardiogenic pulmonary edema: prospective study with a retrospective control group.

BMC Cardiovasc Disord 2007 Dec 20;7:40. Epub 2007 Dec 20.

Thoraxcenter, Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 P.O. Box 30,001, 9700 RB Groningen, The Netherlands.

Background: Continuous positive airway pressure (CPAP) treatment for acute cardiogenic pulmonary edema can have important benefits in acute cardiac care. However, coronary care units are usually not equipped and their personnel not adequately trained for applying CPAP with mechanical ventilators. Therefore we investigated in the coronary care unit setting the feasibility and outcome of the simple Boussignac mask-CPAP (BCPAP) system that does not need a mechanical ventilator.

Methods: BCPAP was introduced in a coronary care unit where staff had no CPAP experience. All consecutive patients transported to our hospital with acute cardiogenic pulmonary edema, a respiratory rate > 25 breaths/min and a peripheral arterial oxygen saturation of < 95% while receiving oxygen, were included in a prospective BCPAP group that was compared with a historical control group that received conventional treatment with oxygen alone.

Results: During the 2-year prospective BCPAP study period 108 patients were admitted with acute cardiogenic pulmonary edema. Eighty-four of these patients (78%) were treated at the coronary care unit of which 66 (61%) were treated with BCPAP. During the control period 66 patients were admitted over a 1-year period of whom 31 (47%) needed respiratory support in the intensive care unit. BCPAP treatment was associated with a reduced hospital length of stay and fewer transfers to the intensive care unit for intubation and mechanical ventilation. Overall estimated savings of approximately euro 3,800 per patient were achieved with the BCPAP strategy compared to conventional treatment.

Conclusion: At the coronary care unit, BCPAP was feasible, medically effective, and cost-effective in the treatment of acute cardiogenic pulmonary edema. Endpoints included mortality, coronary care unit and hospital length of stay, need of ventilatory support, and cost (savings).
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December 2007

Pilot study on the influence of liver blood flow and cardiac output on the clearance of propofol in critically ill patients.

Eur J Clin Pharmacol 2008 Mar 13;64(3):329-34. Epub 2007 Nov 13.

Department of Clinical Pharmacy, St. Antonius Hospital, PO Box 2500, 3430 EM, Nieuwegein, The Netherlands.

Objective: To investigate the effect of cardiac output and liver blood flow on propofol concentrations in critically ill patients in the intensive care unit.

Methods: Five medical/surgical critically ill patients were enrolled in this preliminary study. Liver blood flow was measured using sorbitol. The cardiac output was measured by bolus thermodilution. NONMEM ver. V was applied for propofol pharmacokinetic analysis.

Results: The clearance of propofol was positively influenced by the liver blood flow (P < 0.005), whereas no significant correlation between cardiac output and propofol clearance was found. A correlation between liver blood flow and cardiac output or cardiac index could not be assumed in this patient group.

Conclusions: Liver blood flow is a more predictive indicator than cardiac output for propofol clearance in critically ill patients when the techniques of hepatic sorbitol clearance and bolus thermodilution, respectively, are used. Further study is needed to determine the role played by liver blood flow and cardiac output on the pharmacokinetics of highly extracted drugs in order to reduce the observed high interindividual variabilities in response in critically ill patients.
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March 2008