Paul Soeding

Prospective randomized trial of high thoracic epidural analgesia for coronary artery bypass surgery

BACKGROUND Postoperative pain may be severe after coronary artery bypass surgery. High thoracic epidural analgesia (HTEA) provides intense analgesia. METHODS Eighty patients were randomized to HTEA or intravenous morphine analgesia (control). Patients received coronary artery bypass surgery (CABG) with cardiopulmonary bypass. Pain was measured by visual analogue scale 0 to 10. Psychologic morbidity, intraoperative hemodynamics, ventricular function, lung function, and physiotherapy cooperation were also assessed. On the third postoperative day HTEA and morphine were ceased and only oral medications were used. Acetaminophen, indomethacin, and tramadol were allowed as supplemental analgesics in both groups. RESULTS The primary endpoint of pain scores was significantly less with HTEA on postoperative days 1 and 2 at rest, 0.02 +/- 0.2 versus 0.8 +/- 1.8 (p = 0.008) and 0.1 +/- 0.4 versus 1.2 +/- 2.7 (p = 0.022), respectively, and with coughing 1.2 +/- 1.7 versus 4.4 +/- 3.1 (p < 0.001) and 1.5 +/- 2.0 versus 3.6 +/- 3.1 (p = 0.001), respectively. When HTEA and morphine were ceased on day 3, there were no significant differences. The secondary endpoints of postoperative depression (p = 0.033) and posttraumatic stress subscales (p = 0.021) of the Minnesota Multiphasic Personality Inventory were lower with HTEA. Extubation occurred earlier with HTEA, 2.6 versus 5.4 hours (p < 0.001). HTEA showed improved physiotherapy cooperation (p < 0.001), arterial oxygen tension (p = 0.041), and peak expiratory flow rate (p = 0.001). Mean arterial pressure was lower with HTEA (p = 0.036), otherwise there were no differences in intraoperative hemodynamics or ventricular function. CONCLUSIONS Epidural analgesia reduces pain after coronary operation and is associated with improved physiotherapy cooperation, earlier extubation, and reduced risk of depression and posttraumatic stress.

Routine immediate extubation after cardiac operation: a review of our first 100 patients

BACKGROUND Early extubation after cardiac operation is an important aspect of fast-track cardiac anesthesia. Immediate extubation is an extension of this concept. We describe a technique that allows immediate extubation in the majority of patients. METHODS To allow rapid emergence, anesthesia was modified from a high-dose opioid technique to intravenous propofol anesthesia supplemented with sevoflurane. Normothermic cardiopulmonary bypass was used with routine intermittent antegrade and retrograde tepid blood cardioplegia. High thoracic epidural analgesia was used to facilitate immediate extubation in the majority of patients. Contraindications to immediate extubation were prolonged cardiopulmonary bypass (CPB) (>2.5 hours), hemodynamic instability, uncontrolled bleeding, morbid obesity, severe pulmonary hypertension, congestive cardiac failure, or if the operation was emergent. RESULTS Of 109 consecutive patients, 100 were immediately extubated (92%). No patient required reintubation within the first 24 hours after operation. One patient required reintubation 3 days after operation for sputum retention, and 2 patients required reoperation. There was no mortality and the incidence of perioperative morbidity was low. CONCLUSIONS Immediate extubation after cardiac operation can be safely achieved and is possible in a majority of patients.

Vasoconstrictor Responses to Vasopressor Agents in Human Pulmonary and Radial Arteries An In Vitro Study

Background:Vasopressor drugs, commonly used to treat systemic hypotension and maintain organ perfusion, may also induce regional vasoconstriction in specialized vascular beds such as the lung. An increase in pulmonary vascular tone may adversely affect patients with pulmonary hypertension or right heart failure. While sympathomimetics constrict pulmonary vessels, and vasopressin does not, a direct comparison between these drugs has not been made. This study investigated the effects of clinically used vasopressor agents on human isolated pulmonary and radial arteries. Methods:Isolated pulmonary and radial artery ring segments, mounted in organ baths, were used to study the contractile responses of each vasopressor agent. Concentration–response curves to norepinephrine, phenylephrine, metaraminol, and vasopressin were constructed. Results:The sympathomimetics norepinephrine, phenylephrine, and metaraminol caused concentration-dependent vasoconstriction in the radial (pEC50: 6.99 ± 0.06, 6.14 ± 0.09, and 5.56 ± 0.07, respectively, n = 4 to 5) and pulmonary arteries (pEC50: 6.86 ± 0.11, 5.94 ± 0.05 and 5.56 ± 0.09, respectively, n = 3 to 4). Vasopressin was a potent vasoconstrictor of the radial artery (pEC50 9.13 ± 0.20, n = 3), whereas in the pulmonary artery, it had no significant effect. Conclusions:Sympathomimetic-based vasopressor agents constrict both human radial and pulmonary arteries with similar potency in each. In contrast, vasopressin, although a potent vasoconstrictor of radial vessels, had no effect on pulmonary vascular tone. These findings provide some support for the use of vasopressin in patients with pulmonary hypertension.

Review article: anatomical considerations for ultrasound guidance for regional anesthesia of the neck and upper limb

PurposeThe purpose of this narrative review is to describe an anatomical approach for residents-in-training and anesthesiologists who are learning techniques of ultrasound-guided regional anesthesia of the neck and upper limbSourcesRelevant articles relating anatomy and anatomical variation to the emerging practice of ultrasound-guided regional anesthesia for the neck and upper limb were sourced via both Medline and PubMed databases. Also, our approach to teaching ultrasound technique has developed from using anatomical resources and cadaveric workshops. This approach emphasizes precise image acquisition, a detailed knowledge of anatomy and anatomical variations, and, importantly, visual interpretation of sonographic landmarks based on pattern recognition when interpreting sonograms.Principal findingsTypical sonographic patterns orient the examiner to nerve position, which is necessary for executing successful regional anesthesia of the neck and upper limb. Only by understanding the typical anatomical arrangement can the examiner then visually interpret any individual anatomical variation that may occur.ConclusionSimple sonographic anatomical patterns can provide a strategy to correctly locate nerves when performing ultrasound-guided cervical and brachial plexus anesthesia.RésuméObjectifL’objectif de ce compte-rendu narratif est de décrire une approche anatomique destinée aux résidents en formation et aux anesthésiologistes qui apprennent les techniques d’anesthésie régionale du cou et des membres supérieurs par échoguidage.SourcesLes articles pertinents traitant de l’anatomie et des variations anatomiques dans la pratique émergente de l’anesthésie régionale du cou et des membres supérieurs par échoguidage ont été tirés des bases de données Medline et PubMed. De plus, notre approche de l’enseignement des techniques échoguidées a évolué grâce au recours à des ressources anatomiques et des ateliers sur des cadavres. Cette approche met l’accent sur l’obtention d’images précises, une connaissance détaillée de l’anatomie et des variations anatomiques et, composante importante, l’interprétation visuelle de points de repères échographiques selon une reconnaissance des configurations lors de l’interprétation des échogrammes.Constatations principalesLes configurations échographiques typiques fournissent des informations à l’examinateur quant à la position des nerfs, ce qui est nécessaire à la réalisation d’une anesthésie régionale du cou et des membres supérieurs réussie. Il faut que l’examinateur comprenne la disposition anatomique typique pour ensuite pouvoir interpréter de façon visuelle les variations anatomiques individuelles potentielles.ConclusionDes configurations anatomiques échographiques simples peuvent constituer une bonne stratégie pour localiser correctement les nerfs lors de la réalisation d’une anesthésie cervicale et du plexus brachial par échoguidage.

Effect of phenylephrine on the haemodynamic state and cerebral oxygen saturation during anaesthesia in the upright position

BACKGROUND The upright sitting or beachchair position is associated with hypotension, risk of cerebral hypoperfusion, and cerebral injury. We hypothesized that by increasing arterial pressure with phenylephrine administration, cerebral perfusion, and postoperative recovery would be improved. METHODS Thirty-four patients undergoing elective shoulder surgery were randomized to receive either saline or phenylephrine infusion (PE) 5 min before being placed in the upright position. Simultaneous measurements of mean arterial pressure, cerebral oxygen saturation, middle cerebral artery velocity, and cardiac function using transthoracic echocardiography were made. Postoperative neurocognitive function was assessed. RESULTS At the commencement of PE, mean (SD) cerebral oxygen saturation significantly decreased from 77 (10) to 67 (13)% (P=0.02), and further to 59 (11) % on upright positioning. The level of cerebral saturation upright was not significantly different to patients receiving saline (P=0.07), with values remaining at room-air levels. Middle cerebral artery blood velocity increased by 20% (P=0.04). Phenylephrine prevented hypotension in the upright position primarily by maintaining preload and increasing systemic vascular resistance (P=0.01), and was associated with a decrease in cardiac output. No postoperative neurocognitive dysfunction was identified. CONCLUSIONS Despite maintaining arterial pressure with phenylephrine, cerebral desaturation occurred with upright positioning. Cerebral oxygen saturation can provide a valuable endpoint when evaluating the effect of vasopressor therapy on cerebral perfusion.

Levosimendan preserves the contractile responsiveness of hypoxic human myocardium via mitochondrial KATP channel and potential pERK 1/2 activation

This study investigated the role of levosimendan, a mitochondrial K(ATP) channel opener, during hypoxia-reoxygenation injury in human isolated tissue. The activation of preconditioning pathways, and the release of mitochondrial cytochrome c were determined. Human right atrial trabeculae were mounted in an organ bath, electrically paced and contractile force measured. Tissue was subjected to hypoxia-reoxygenation, and isoproterenol concentration-response experiments were performed as an index of contractile viability. The intracellular activities of Akt, ERK 1/2, P38, caspase 3, and cytochrome c were assayed by western blot. Following hypoxia-reoxygenation, the maximal contractile response of trabeculae to isoproterenol was significantly increased with levosimendan pretreatment compared to the hypoxia-reoxygenation control (0.88±0.02 versus 0.60±0.01g, P<0.01). This enhanced response was blocked by 5-hydroxydecoanate (0.54±0.09g, P<0.01). A significant increase in both phosphorylated and total ERK 1/2 and P38 occurred at 60min reoxygenation, compared to control tissue. No difference was observed in phosphorylated or total Akt, though there was a trend for increased levels in hypoxic tissue. Cytochrome c was detected at 60min post reoxygenation, in both levosimendan treated and untreated tissue. No increase in cleaved-caspase 3 activity was observed. Our findings suggest that levosimendan preserves the contractile force to isoproterenol after hypoxia-reoxygenation, a response mediated via mK(ATP) channel activation. The significant increase in the activity of prosurvival mediators ERK 1/2 and P38 following hypoxia indicates a potential mechanism of action for levosimendan-induced cardioprotection.

The role of voltage-operated and non-voltage-operated calcium channels in endothelin-induced vasoconstriction of rat cerebral arteries

Endothelin-1 has been identified as a potential mediator in the pathogenesis of ischaemic stroke and cerebral vasospasm. The aim of this study was to analyse the role of voltage-operated calcium channels (VOCC) and non-VOCC in endothelin-1 induced vasoconstriction of rat cerebral arteries. Arterial segments were dissected from different regions of the cerebral circulation and responses assessed using wire myography. Endothelin-1 concentration-contraction curves were constructed in calcium-free medium or in the presence of nifedipine, NNC 55-0396 ((1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride) or SK&F 96365 (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole) to inhibit the l-type VOCC, T-type VOCC and non-VOCC, respectively. Inhibition of the calcium channels or removal of calcium from the medium variably decreased the maximum effects (Emax) of endothelin-1, however its potency (pEC50) was unaltered. Endothelin-1 caused a small contraction (<22%) in calcium-free solution. Pre-treatment with nifedipine (1µM) did not affect responses to low concentrations of endothelin-1 but decreased Emax, while NNC 55-0396 (1µM) and SK&F 96365 (30-100µM) generally attenuated the endothelin-1-induced contraction. Combination of nifedipine with SK&F 96365 further decreased the Emax. The relaxant effect of the calcium channel antagonists was also assessed in pre-contracted arteries. Only nifedipine and SK&F 96365 relaxed the arteries pre-contracted with endothelin-1. In conclusion, VOCC and non-VOCC calcium channels are involved in different phases of the endothelin-1 contraction in rat cerebral vessels. T-type VOCC may be involved in contraction induced by low concentrations of endothelin-1, while l-type VOCC mediate the maintenance phase of contraction. VOCC and non-VOCC may work in concert in mediating contraction induced by endothelin-1.

Sustained cardiac programming by short‐term juvenile exercise training in male rats

Cardiac hypertrophy following endurance‐training is thought to be due to hypertrophy of existing cardiomyocytes. The benefits of endurance exercise on cardiac hypertrophy are generally thought to be short‐lived and regress to sedentary levels within a few weeks of stopping endurance training. We have now established that cardiomyocyte hyperplasia also plays a considerable role in cardiac growth in response to just 4 weeks of endurance exercise in juvenile (5–9 weeks of age) rats. The effect of endurance exercise on cardiomyocyte hyperplasia diminishes with age and is lost by adulthood. We have also established that the effect of juvenile exercise on heart mass is sustained into adulthood.

Evaluation of right heart function in a rat model using modified echocardiographic views

Echocardiography plays a major role in assessing cardiac function in animal models. We investigated use of a modified parasternal mid right-ventricular (MRV) and right ventricle (RV) outflow (RVOT) view, in assessing RV size and function, and the suitability of advanced 2D-strain analysis. 15 WKY rats were examined using transthoracic echocardiography. The left heart was assessed using standard short and long axis views. For the right ventricle a MRV and RVOT view were used to measure RV chamber and free wall area. 2D-strain analysis was applied to both ventricles using off-line analysis. RV chamber volume was determined by injection of 2% agarose gel, and RV free wall dissected and weighed. Echocardiography measurement was correlated with necropsy findings. The RV mid-ventricular dimension (R1) was 0.42±0.07cm and the right ventricular outflow tract dimension (R2) was 0.34±0.06cm, chamber end-diastolic area measurements were 0.38±0.09cm2 and 0.29±0.08cm2 for MRV and RVOT views respectively. RVOT and MRV chamber area correlated with gel mass. Doppler RV stroke volume was 0.32±0.08ml, cardiac output (CO) 110±27 ml.min-1 and RV free wall contractility assessed using 2D-strain analysis was demonstrated. We have shown that modified MRV and RVOT views can provide detailed assessment of the RV in rodents, with 2D-strain analysis of the RV free wall potentially feasible.

Functional estimation of endothelin-1 receptor antagonism by bosentan, macitentan and ambrisentan in human pulmonary and radial arteries in vitro

Background Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ETA‐receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically‐approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro. Methods Human isolated pulmonary (i.d. 5.5 mm) and human radial (i.d. 3.23 mm) artery ring segments were mounted in organ baths for isometric force measurement. Single concentration‐contraction curves to endothelin‐1 were constructed in the absence or presence of bosentan (1–10 &mgr;M), macitentan (0.03–0.3 &mgr;M) or ambrisentan (0.1–1 &mgr;M). Results All 3 endothelin antagonists caused competitive rightward shifts in the endothelin‐1 concentration‐response curves in both arteries. The Clark plot and analysis gave the following pKB values: bosentan, pulmonary artery 6.28±0.13 and radial artery 6.04±0.10; macitentan, pulmonary artery 8.02±0.13 and radial artery 7.49±0.08; and ambrisentan, pulmonary artery 7.38±0.13 and radial artery 6.96±0.10. Conclusions Noting the maximum plasma levels attained from recommended oral doses of each antagonist in volunteers, the pKB findings here show that there would be significant antagonism of endothelin‐1 contraction in the pulmonary and radial arteries at therapeutic plasma levels. This functional assay confirms in human tissue that much higher plasma concentrations of endothelin‐1 receptor antagonists are required to be effective than those predicted from binding or other biochemical assays.