Thomas Mollhoff

High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting.

UNLABELLED In this prospective study, we evaluated whether high thoracic epidural anesthesia (TEA) or i.v. clonidine, in addition to general anesthesia, affects the cardiopulmonary bypass- and surgery-associated stress response and incidence of myocardial ischemia by their sympatholytic properties. Seventy patients scheduled for elective coronary artery bypass graft (CABG) received general anesthesia with sufentanil and propofol. TEA was randomly induced before general anesthesia and continued during the study period in 25 (anesthetized dermatomes C6-T10). Another 24 patients received i.v. clonidine as a bolus of 4 microg/kg before the induction of general anesthesia. Clonidine was then infused at a rate of 1 microg x kg(-1) x h(-1) during surgery and at 0.2-0.5 microg x kg(-1) x h(-1) postoperatively. The remaining 21 patients underwent general anesthesia as performed routinely (control). Hemodynamics, plasma epinephrine and norepinephrine, cortisol, the myocardial-specific contractile protein troponin T, and other cardiac enzymes were measured pre- and postoperatively. During the preoperative night and a follow-up of 48 h after surgery, five-lead electrocardiogram monitoring was used for ischemia detection. Both TEA and clonidine reduced the postoperative heart rate compared with the control group without jeopardizing cardiac output or perfusion pressure. Plasma epinephrine increased perioperatively in all groups but was significantly lower in the TEA group. Neither TEA nor clonidine affected the increase in plasma cortisol. The release of troponin T was attenuated by TEA. New ST elevations > or = 0.2 mV or new ST depression > or = 0.1 mV occurred in > 70% of the control patients but only in 40% of the clonidine group and in 50% of the TEA group. We conclude that TEA (but not i.v. clonidine) combined with general anesthesia for CABG demonstrates a beneficial effect on the perioperative stress response and postoperative myocardial ischemia. IMPLICATIONS Thoracic epidural anesthesia combined with general anesthesia attenuates the myocardial sympathetic response to cardiopulmonary bypass and cardiac surgery. This is associated with decreased myocardial ischemia as determined by less release of troponin T. These findings may have an impact on the anesthetic management for coronary artery bypass grafting.

Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting

BACKGROUND Although patients with reduced left ventricular ejection fraction undergoing cardiac operation experience a higher rate of perioperative complications, the contribution of proinflammatory cytokines released during extracorporeal circulation is not well defined. METHODS We compared arterial and mixed venous levels of interleukin-6, tumor necrosis factor-alpha, soluble interleukin-2 receptor, and interleukin-2 at 10 points in time (24 hours before until 48 hours after extracorporeal circulation) in 21 patients with an ejection fraction of less than 0.45 (study group) to 15 patients with an ejection fraction of more than 0.55 (control group) undergoing elective coronary artery bypass grafting. The study and control group differed with regard to left ventricular ejection fraction (0.37 +/- 0.05 versus 0.66 +/- 0.11, p < 0.05) and reperfusion time (35 +/- 42 minutes versus 18 +/- 4 minutes, p = 0.07), but not age, sex, vessel involvement, number of grafts performed, cross-clamp time, extracorporeal circulation time, core temperature, and duration of ventilation. RESULTS Six patients in the study group required mechanical support and 1 died. There were no complications in the control group. In the study group, there were higher preoperative interleukin-2 and tumor necrosis factor-alpha levels and a higher maximum cytokine response to extracorporeal circulation for interleukin-2, soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha (all p < 0.05). Interleukin-6 correlated with duration of extracorporeal circulation, dose of norepinephrine and epinephrine support, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, right atrial pressure, heart rate, cardiac index, and inversely with systemic vascular resistance. Interleukin-6 was highest in patients with complications. Arterial and venous cytokine levels correlated closely. CONCLUSIONS Preoperative left ventricular dysfunction is associated with a higher degree of proinflammatory cytokine release during elective coronary artery bypass grafting. This response is associated with impaired hemodynamics and a higher incidence of perioperative complications.

Epidural analgesia with local anesthetics after abdominal surgery : Earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine

UNLABELLED The aim of this prospective, randomized, double-blinded study was to compare pain relief, side effects, and ability to ambulate during epidural anesthesia with ropivacaine 0.2% plus sufentanil versus bupivacaine 0.175% plus sufentanil after major gastrointestinal surgery. Epidural catheters were inserted at T8-11, and 30 microg of sufentanil with 15 mL of ropivacaine 0.75% (Group 1, n = 42) or bupivacaine 0.5% (Group 2, n = 44) was injected. General anesthesia was induced, a continuous epidural infusion (5 mL/h) was then begun with 1 microg/mL sufentanil plus ropivacaine 0.2% (Group 1) or bupivacaine 0.175% (Group 2). Postoperatively, the infusion rate was adjusted to individual requirements. Patients were also able to receive additional 2-mL bolus doses every 20 min. Demographic data (except for gender and height), analgesia, drug dosage, and side-effects, including motor blockade (Bromage score), were similar in both groups, but mobilization recovered more quickly in Group 1. Gender, age, ASA physical status, duration of surgery, and intraoperative blood loss had no effect on mobilization. We conclude that epidural analgesia is effective and safe with both regimens. There is not necessarily a correlation between the Bromage score and the desired outcome of mobilization. The ability to walk postoperatively is hastened if ropivacaine is used instead of bupivacaine. IMPLICATIONS Regarding pain relief and side effects, epidural analgesia with ropivacaine 0.2% and sufentanil 1 microg/mL yields pain scores and pain intensity comparable to those for the well evaluated combination of bupivacaine 0.175% and sufentanil 1 microg/mL. However, earlier recovery of the ability to walk unassisted in patients receiving the combination of ropivacaine and sufentanil may result in their earlier rehabilitation.

Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia using Org 10172.

BACKGROUND In patients with heparin-induced thrombocytopenia undergoing cardiac operations, anticoagulation with heparin should be avoided. The low-molecular-weight glycosaminoglycan Orgaran has been used as an alternative, but the overall experience is limited. METHODS Two patients with heparin-induced thrombocytopenia underwent cardiopulmonary bypass using Orgaran for anticoagulation. A 30-year-old woman suffered from emboli to her brain through a secondary atrial septal defect, a 14-year-old boy from ischemia of his left leg due to recurrent embolism originating from the mitral valve. In both cases, cardiopulmonary bypass was performed in a routine manner, except for using low-dose Orgaran instead of heparin. Anticoagulation was monitored during cardiopulmonary bypass by measuring Orgaran plasma levels and activated clotting time. RESULTS No thromboembolic or bleeding complications occurred during and after atrial septal defect repair and mitral valve replacement, respectively. In the former case, thrombotic material from the inferior vena cava was removed during hypothermic circulatory arrest within the same procedure. Activated clotting time did not correlate with plasma levels of Orgaran. CONCLUSIONS Orgaran might be a useful alternative for anticoagulation during extracorporeal circulation. Adequate dosages and measurement of plasma levels are recommended for its use in cardiopulmonary bypass.

Milrinone Modulates Endotoxemia, Systemic Inflammation, and Subsequent Acute Phase Response after Cardiopulmonary Bypass (CPB)

BACKGROUND Compromised splanchnic perfusion and the resulting intestinal mucosal injury leads to a decreased mucosal barrier function, which allows translocation of intestinal flora and endotoxemia. The authors evaluated the effects of milrinone on splanchnic oxygenation, systemic inflammation, and the subsequent acute-phase response in patients undergoing coronary artery bypass grafting. METHODS This open, placebo-controlled randomized clinical study enrolled 22 adult patients in two groups. Before induction of anesthesia, baseline values were obtained and patients were randomized to receive milrinone (30 microg/kg bolus administered progressively in 10 min, followed by a continuous infusion of 0.5 microg x kg(-1) x min(-1)) or saline. The following parameters were determined: hemodynamics; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; intramucosal pH (pHi); and mixed and hepatic venous plasma concentrations of endotoxin, interleukin 6, serum amyloid A, and C-reactive protein. RESULTS Milrinone did not prevent gastrointestinal acidosis as measured by pHi, but its perioperative administration resulted in significantly higher pHi levels compared with control. Venous and hepatic venous endotoxin and the interleukin 6 concentration were reduced significantly in the milrinone group. Serum amyloid A values were attenuated in the milrinone group 24 h after surgery. No significant differences could be seen in routinely measured oxygen transport-derived variables. CONCLUSIONS Perioperative administration of low-dose milrinone may have antiinflammatory properties and may improve splanchnic perfusion in otherwise healthy patients undergoing routine coronary artery bypass grafting.

The Inhibitory Effect of Bupivacaine on Prostaglandin E 2 (EP 1 ) Receptor Functioning: Mechanism of Action

Prostaglandin E2 receptors, subtype EP1 (PGE2EP1) have been linked to several physiologic responses, such as fever, inflammation, and mechanical hyperalgesia. Local anesthetics modulate these responses, which may be due to direct interaction of local anesthetics with PGE2EP1 receptor signaling. We sought to characterize the local anesthetic effects on PGE2EP1 signaling and elucidate mechanisms of anesthetic action. In Xenopus laevis oocytes, recombinant expressed PGE2EP1 receptors were functional (half maximal effect concentration, 2.09 ± 0.98 × 10−6 M). Bupivacaine, after incubation for 10 min, inhibited concentration-dependent PGE2EP1 receptor functioning (half-maximal inhibitory effect concentration, 3.06 ± 1.26 × 10−6 M). Prolonged incubation in bupivacaine (24 h) inhibited PGE2-induced calcium-dependent chloride currrents (ICl(Ca)) even more. Intracellular pathways were not significantly inhibited after 10 min of incubation in bupivacaine. But ICl(Ca) activated by intracellular injection of GTP&ggr;S (a nonhydrolyzable guanosine triphosphate [GTP] analog that activates G proteins, irreversible because it cannot be dephosphorylated by the intrinsic GTPase activity of the &agr; subunit of the G protein) was reduced after 24 h of incubation in bupivacaine, indicating a G protein-dependent effect. However, inositol 1,4,5-trisphosphate- and CaCl2- induced ICl(Ca) were unaffected by bupivacaine at any time points tested. Therefore, bupivacaine’s effect is at phospholipase C or at the G protein or the PGE2EP1 receptor. All inhibitory effects were reversible. We conclude that bupivacaine inhibited PGE2EP1 receptor signaling at clinically relevant concentrations. These effects could, at least in part, explain how local anesthetics affect physiologic responses such as fever, inflammation, and hyperalgesia during the perioperative period.

Cardiopulmonary effects of enoximone or dobutamine and nitroglycerin on mitral valve regurgitation and pulmonary venous hypertension

OBJECTIVE To compare the cardiovascular and pulmonary effects of the phosphodiesterase III inhibitor enoximone (EN) or a combination of dobutamine (DOB) and nitroglycerin (NTG) before and after mitral valve repair or replacement. DESIGN Prospective, randomized, controlled clinical study. SETTING University hospital. PARTICIPANTS Twenty patients with mitral regurgitation and pulmonary venous hypertension scheduled for elective mitral valve surgery. INTERVENTIONS Patients fulfilling the inclusion criteria of the study were randomly allocated into a group treated with EN (group 1, n = 10) or DOB and NTG (group 2, n = 10). A cardiopulmonary status was obtained after induction of anesthesia and mechanical ventilation during stable hemodynamic conditions (control). Then the patients received either EN (bolus dose 1.0 mg/kg followed by a continuous infusion of 10 micrograms/kg/min) or DOB (8.0 micrograms/kg/min) and NTG (1.0 microgram/kg/min) according to the randomization. After a period of 20 minutes, all parameters were measured again. The study drugs were stopped, and cardiac surgery was performed. Infusions of EN (without additional loading dose) or DOB and NTG were started again in the above-described doses 10 minutes before separation from cardiopulmonary bypass (CPB). Respiratory and hemodynamic measurements were made 20 minutes after weaning from CPB and 60 minutes after admission of the patient to the intensive care unit. MEASUREMENTS AND MAIN RESULTS Both groups were comparable regarding preoperative and control data. Before mitral valve surgery, cardiac output (CO) and heart rate (HR) increased by 46% (p < 0.05) and 31% (p < 0.01) during infusion of EN with minor changes of mean systemic arterial pressure (PSA) and gas exchange. Mean pulmonary arterial pressure (PPA) decreased from 32 +/- 11 mmHg to 23 +/- 11 mmHg (p < 0.05). Similar alterations were observed in group 2 (delta CO + 26%, p < 0.05, delta HR + 39%, p < 0.01); however, PPA and calculated pulmonary vascular resistance remained unchanged. After separation from CPB, EN and DOB-NTG achieved comparable effects on CO, HR, and PSA, but PPA was significantly lower in group 1. In addition, venous admixture and alveolo-arterial oxygen tension gradient were lower in EN-treated patients. CONCLUSION Enoximone or DOB and NTG have comparable effects on CO, PSA, and HR in mitral regurgitation and pulmonary hypertension, but EN is more effective in reducing PPA without deterioration of gas exchange.

The effects of thoracic epidural anesthesia on functional recovery from myocardial stunning in propofol-anesthetized dogs.

The purpose of this investigation was to examine the effects of thoracic epidural anesthesia (TEA) on myocardial stunning during propofol anesthesia.Six dogs were chronically instrumented for measurement of left atrial, aortic, and left ventricular pressure, maximal rate of increase of left ventricular pressure, and myocardial wall-thickening fraction (WTF). Myocardial blood flow was determined with colored microspheres. Experiments were performed on separate days with 1) 10 min of left anterior descending artery (LAD) ischemia during propofol anesthesia without TEA, and 2) 10 min of LAD ischemia during propofol anesthesia with TEA. WTF was measured as baseline (BL) prior to propofol anesthesia and at predetermined time points until complete recovery from stunning. Propofol anesthesia caused a significant decrease of WTF in the LAD-perfused myocardium (LAD-WTF) compared to BL in awake animals. LAD ischemia led to a further significant decrease of LAD-WTF. There were no significant differences in LAD-WTF between the two experimental conditions at any of the time points measured. TEA did not change subendocardial blood flow in nonischemic myocardium. During ischemia neither the subendocardial/subepicardial nor the occluded/normal zone blood flow ratio were affected by TEA. After myocardial ischemia during propofol anesthesia TEA does not affect functional recovery of stunned myocardium in dogs. (Anesth Analg 1997;84:723-9)

Laienreanimation – Reanimation als Schulfach: „Was Hänschen nicht lernt …“

Sudden cardiac arrest is a major contributor to avoidable deaths in Europe. Immediate start of basic life support (BLS) by laypersons is among the most successful strategies in the treatment of cardiac arrest patients. Despite the fact that more than half of all cardiac arrests in Germany are witnessed by a bystander, only in one fifth of all arrests layperson resuscitation is initiated. One strategy to enhance bystander BLS is to establish cardiac resuscitation tuition in schools. BLS instructions for pupils have been proven to be successfully implemented independent from childrens age or physical ability. Although an age-adjusted curriculum seems reasonable even usage of automatic external defibrillators (AED) can be taught effectually. The earlier in the life of a student BLS-instruction begins, the more successful the training is. However a national German curriculum for BLS-training in schools has yet to be established in Germany.

Experimental arthritis in the rat does not alter the analgesic potency of intrathecal or intraarticular morphine.

UNLABELLED To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (i.a.) or intrathecal (i.t) morphine in tests of thermal and mechanical nociception changed during the induction of experimental arthritis in the rat. Thermal nociception by i.t. morphine (3, 10, and 50 micrograms) or i.a. morphine (100, 1000, and 3000 micrograms) was assessed by means of a modified Hargreaves box ever) 28 h. Mechanical antinociception was determined for the largest applied doses of morphine using von Frey hairs. Morphine produced dose-dependent thermal antinociception after i.t. or i.a. administration: a 50% increase in maximum antinociceptive thermal response (50% effective dose) was produced by i.t. doses of 9.7 micrograms at the start and 9.1 micrograms at the end of this 28-h observational interval, whereas after i.a. administration, 50% effective dose values were 553 micrograms at the start and 660 micrograms at the end. The largest applied dose of either i.t. or i.a. morphine produced mechanical antinociception. On Day 1, the antinociceptive effect for mechanical nociception (expressed as the area under the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for i.t. morphine 50 micrograms and 53% for i.a. morphine 3000 micrograms. Neither result differed from the corresponding area under the curve values on Day 2. Naloxone administered either i.t. or i.a. abolished the antinociceptive action of morphine given at the same site. We conclude that, although morphine has a peripheral analgesic site of action in a rat arthritis model, its potency for both i.a. and i.t. routes of administration does not change during the onset of arthritis. IMPLICATIONS In this animal study, we showed that the administration of morphine modulates thermal and mechanical antinociception at central and peripheral sites in inflammatory pain.