Hendrik Freise

Risks and benefits of thoracic epidural anaesthesia

Thoracic epidural anaesthesia (TEA) reduces cardiac and splanchnic sympathetic activity and thereby influences perioperative function of vital organ systems. A recent meta-analysis suggested that TEA decreased postoperative cardiac morbidity and mortality. TEA appears to ameliorate gut injury in major surgery as long as the systemic haemodynamic effects of TEA are adequately controlled. The functional benefit in fast-track and laparoscopic surgery needs to be clarified. Better pain control with TEA is established in a wide range of surgical procedures. In a setting of advanced surgical techniques, fast-track regimens and a low overall event rate, the number needed to treat to prevent one death by TEA is high. The risk of harm by TEA is even lower, and other methods used to control perioperative pain and stress response also carry specific risks. To optimize the risk-benefit balance of TEA, safe time intervals regarding the use of concomitant anticoagulants and consideration of reduced renal function impairing their elimination must be observed. Infection is a rare complication and is associated with better prognosis. Close monitoring and a predefined algorithm for the diagnosis and treatment of spinal compression or infection are crucial to ensure patient safety with TEA. The risk-benefit balance of analgesia by TEA is favourable and should foster clinical use.

Arginine vasopressin compromises gut mucosal microcirculation in septic rats

ObjectiveArginine vasopressin (AVP) is increasingly used in the therapy of septic patients with hypotension. However, its effects on the microvascular networks have not been studied in detail. This study was designed to determine the effects of AVP infusion on the villus microcirculation of the septic rat ileum. DesignProspective, placebo-controlled, randomized, single-blinded trial. SettingUniversity research laboratory. SubjectsFifteen male Sprague-Dawley rats. InterventionsTwenty-four hours after cecal ligation and perforation to create sepsis (M1), rats (n = 8) received a continuous AVP infusion to increase mean arterial pressure by 20 mm Hg (M2) and 40 mm Hg (M3) from M1. In the control group (n = 7), an equivalent volume of normal saline was infused. Measurements and Main ResultsVideomicroscopy was performed on 6–10 villi of ileum mucosa at M1 and was repeated at M2 and M3. Blood was drawn to determine plasma levels of AVP and interleukin-6. At M1, both study groups were hypotensive compared with preseptic data (mean arterial pressure, −25%). The increase in mean arterial pressure was linked to supraphysiologic AVP plasma levels and was accompanied by a decrease in mean mucosal blood flow by 76% at M2 and 81% at M3 (p < .001 vs. control). Red blood cell velocity fell by 45% and 47%, respectively (p < .05 vs. control). Whereas periods of arrested villus blood flow increased from 8.1 ± 2.6 secs/min to 43.8 ± 5.2 and 47 ± 6.2 secs/min at M2 and M3 (p < .001), the diameter of terminal arterioles remained unchanged. In addition, AVP infusion further augmented the sepsis-associated increase in interleukin-6 levels (AVP, 905 ± 160 vs. control, 638 ± 55 pg/mL; p = .022). ConclusionsThis study provides evidence for severe abnormalities in gut mucosal blood flow after AVP infusion in septic rats, accompanied by an augmented inflammatory response to the septic injury. The effects of AVP on microvascular blood flow in this model may be related to AVP activities on larger arterioles (>40 &mgr;m), a concomitant reduction in cardiac output, or even both.

Hypoglycemia Aggravates Critical Illness-Induced Neurocognitive Dysfunction

OBJECTIVE Tight glycemic control (TGC) in critically ill patients is associated with an increased risk of hypoglycemia. Whether those short episodes of hypoglycemia are associated with adverse morbidity and mortality is a matter of discussion. Using a case-control study design, we investigated whether hypoglycemia under TGC causes permanent neurocognitive dysfunction in patients surviving critical illness. RESEARCH DESIGN AND METHODS From our patient data management system, we identified adult survivors treated for >72 h in our surgical intensive care unit (ICU) between 2004 and 2007 (n = 4,635) without a history of neurocognitive dysfunction or structural brain abnormalities who experienced at least one episode of hypoglycemia during treatment (hypo group) (n = 37). For each hypo group patient, one patient stringently matched for demographic- and disease-related data were identified as a control subject. We performed a battery of neuropsychological tests investigating five areas of cognitive functioning in both groups at least 1 year after ICU discharge. Test results were compared with data from healthy control subjects and between groups. RESULTS Critical illness caused neurocognitive dysfunction in all tested domains in both groups. The dysfunction was aggravated in hypo group patients in one domain, namely that of visuospatial skills (P < 0.01). Besides hypoglycemia, both hyperglycemia (r = −0.322; P = 0.005) and fluctuations of blood glucose (r = −0.309; P = 0.008) were associated with worse test results in this domain. CONCLUSIONS Hypoglycemia was found to aggravate critical illness–induced neurocognitive dysfunction to a limited, but significant, extent; however, an impact of hyperglycemia and fluctuations of blood glucose on neurocognitive function cannot be excluded.

Thoracic Epidural Analgesia Augments Ileal Mucosal Capillary Perfusion and Improves Survival in Severe Acute Pancreatitis in Rats

Background:Acute pancreatitis has been linked to intestinal barrier dysfunction and systemic inflammatory response with high mortality. Thoracic epidural analgesia improves intestinal perfusion. The authors hypothesized that thoracic epidural analgesia influences microcirculation injury, inflammatory response, and outcome of acute pancreatitis in rats. Methods:Control groups underwent a sham procedure or untreated pancreatitis induced by intraductal taurocholate injection. In the treatment groups, epidural analgesia was commenced immediately or after a 7-h delay. Fifteen hours after injury, the ileal mucosal perfusion was assessed by intravital microscopy. Thereby, the intercapillary area between all perfused capillaries and between continuously perfused capillaries only was used to differentially quantify total and continuous capillary mucosal perfusion. Villus blood flow and serum levels of amylase, lactate, and interleukin 6 were determined, and pancreatic injury was scored histologically. Seven-day survival was recorded in an additional 30 rats undergoing untreated pancreatitis or pancreatitis with epidural analgesia. Results:In untreated pancreatitis, decreased total capillary perfusion increased the total intercapillary area by 24%. Furthermore, loss of continuous perfusion increased continuous intercapillary area to 228%. After immediate and delayed epidural analgesia, continuous perfusion was restored (P < 0.05). Blood flow decreased 50% in untreated pancreatitis but was preserved by epidural analgesia (P < 0.05). Biochemical and histologic signs of pancreatitis were not affected by epidural analgesia. Lactate and interleukin-6 levels increased in untreated pancreatitis, which was prevented in the treatment groups (P < 0.05). Epidural analgesia increased 7-day survival from 33% to 73% (P < 0.05). Conclusion:Thoracic epidural analgesia attenuated systemic response and improved survival in severe acute pancreatitis. These effects might be explained by improved mucosal perfusion.

Thoracic epidural analgesia with low concentration of bupivacaine induces thoracic and lumbar sympathetic block: a randomized, double-blind clinical trial.

Background:Clinical benefits of thoracic epidural anesthesia (TEA) are partly ascribed to thoracic sympathetic block. However, data regarding sympathetic activity during TEA are scarce and contradictory. This prospective, randomized, double-blind study evaluated the segmental propagation of sympathetic block after low-concentration, high-volume TEA using digital thermography. Methods:Twenty-four patients were included in the study. Thoracic epidural catheters were placed at a median insertion level of T8–T9. Patients were accommodated for 20 min to the room temperature of 23° ± 0.3°C. Skin temperature was recorded by digital thermography. After baseline measurement of heart rate, arterial pressure, and core body and skin temperature, 10 ml saline (control group) or 10 ml bupivacaine, 0.25% (TEA group), respectively, was administered epidurally. Five minutes (t5) and 20 min (t20) after baseline measurements, hemodynamic parameters and core body temperature were again measured, and sensory block was identified by loss of cold–warm discrimination. In the thumb, the toe, and each thoracic dermatome, difference from baseline temperature was calculated at t5 and t20. Data were analyzed by Mann–Whitney U test. Results:Baseline characteristics did not differ among groups. Median spread of sensory block at t20 was T5–L5. At both t5 and t20, skin temperature decreased more in the control group than in the TEA group in all thoracic dermatomes (P < 0.05). Toe temperature increased in the TEA group compared with the control group (P < 0.05), whereas thumb temperature remained unchanged. Conclusion:TEA with 10 ml bupivacaine, 0.25%, induced thoracic and lumbar sympathetic block that precedes and exceeds sensory block. Caudal limit of sympathetic block could not be demonstrated in this study.

Efficacy of intravenous paracetamol compared to dipyrone and parecoxib for postoperative pain management after minor-to-intermediate surgery: a randomised, double-blind trial.

Background and objective Paracetamol has a well established pharmacological profile, but its postoperative efficacy is in question. This double-blind, placebo-controlled study was designed to compare the efficacy of intravenous paracetamol with other intravenous non-opioids as part of a multimodal concept for perioperative pain therapy. Methods Patients undergoing minor-to-intermediate surgery under general anaesthesia were randomly assigned to receive infusions of paracetamol (1 g every 6 h), dipyrone (1 g every 6 h), parecoxib (40 mg every 12 h) separated by infusions of physiological saline 0.9%, or placebo (0.9% saline every 6 h), respectively, for at least 48 h as part of a multimodal pain concept. Patient-controlled piritramide was administered as rescue medication. Dependent variables were recorded 1, 6, 18, 30 and 42 h after extubation and 1 week after surgery. Surgical and associated pain was scored as the primary outcome on a visual analogue scale. Additionally, time to first dose and total piritramide dosage, satisfaction, respiratory depression, nausea, vomiting, sedation, itching and sweating were recorded. Results A total of 196 patients were recruited. The efficacy of paracetamol was similar to that of the other non-opioid analgesics. Surgical pain was reduced with all non-opioids compared to placebo; there was no effect on associated pain. Piritramide dosage and incidence of side effects were not reduced. Conclusion Intravenous paracetamol has equivalent efficacy to non-opioids dipyrone and parecoxib that improves postoperative pain therapy when used as part of a multimodal concept after minor-to-intermediate surgery.

Continuous thoracic epidural anesthesia improves gut mucosal microcirculation in rats with sepsis.

Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. The present study was designed as a prospective and controlled laboratory experiment to assess the effects of continuous TEA on the mucosal microcirculation in a cecal ligation and perforation model of sepsis in rats. Anesthetized Sprague-Dawley rats underwent laparotomy and cecal ligation and perforation to induce sepsis. Subsequently, either bupivacaine 0.125% (n = 10) or isotonic sodium chloride solution (n = 9) was continuously infused via the thoracic epidural catheter for 24 h. In addition, a sham laparotomy was carried out in eight animals. Intravital videomicroscopy was then performed on six to ten villi of ileum mucosa. The capillary density was measured as areas encircled by perfused capillaries, that is, intercapillary areas. The TEA accomplished recruitment of microcirculatory units in the intestinal mucosa by decreasing total intercapillary areas (1,317 ± 403 vs. 1,001 ± 236 μm2) and continuously perfused intercapillary areas (1,937 ± 512 vs. 1,311 ± 678 μm2, each P < 0.05). Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.

Altered Blood Flow in Terminal Vessels After Local Application of Ropivacaine and Prilocaine

Background Ropivacaine is primarily a local anesthetic, but it also acts as a vasoactive agent. Case reports have described a critical reduction in blood flow when higher concentrations of ropivacaine were used for peripheral-nerve blocks. One hypothesis is that local application of ropivacaine in tissues supplied by end arteries reduces tissue blood flow because of arterial vasoconstriction. Methods Rats were anesthetized by inhalation of isoflurane. The tail vessels were carefully dissected from the ventral side near the radix. Randomly, normal saline, prilocaine 0.5%, prilocaine 0.5% with epinephrine 1:200,000, ropivacaine 0.2%, ropivacaine 0.5%, or ropivacaine 0.75% was applied directly to the artery. Blood flow in the tail was continuously measured by use of laser Doppler flowmetry distal to the surgical site. Changes in temperature in the tail were detected by use of infrared thermography. Results Blood flow decreased after the application of ropivacaine at all concentrations in comparison with normal saline (P < .01 at t = 10 minutes, P < .001 at t = 20, 30, and 40 minutes). This effect was most pronounced at t = 30 minutes for ropivacaine 0.5% (with a 64.5% decrease in blood flow). Prilocaine 0.5% with epinephrine 1:200,000 reduced blood flow by up to 44.7% (t = 20 minutes, P < .001). In comparison with the placebo, the application of ropivacaine 0.5% and 0.75%, as well as prilocaine 0.5% with epinephrine 1:200,000, caused a significant reduction in tail temperature (P < .001 at t = 20, 30, and 40 minutes). No alteration in blood flow or temperature was seen after application of prilocaine 0.5%. Conclusions The application of ropivacaine directly to a rats tail artery diminished blood flow and lowered regional skin temperature. These effects were dose related. The use of ropivacaine at higher concentrations can, therefore, not be recommended if tissues supplied by end arteries might be affected.

Continuous thoracic epidural anesthesia induces segmental sympathetic block in the awake rat.

Thoracic epidural anesthesia (TEA) is used increasingly in critical care, especially for cardiac and intestinal sympathetic block. In this study we evaluated cardiorespiratory function and sympathetic activity in a new model of continuous TEA in awake rats. Thirteen rats received epidural saline control (CON) or bupivacaine 0.5% epidural infusion (EPI) at 15 &mgr;l/h for 2 h on day 1 and day 3. Mean arterial blood pressure, heart rate, respiration rate, arterial Pco2, and motor score were recorded at baseline and after 30, 60, 90, and 120 min. Skin temperature was measured at front paws, high-thoracic, mid-thoracic, and low-thoracic, hind paws, and the proximal and distal tail. Changes in sympathetic activity were assessed by skin temperature changes from baseline (&Dgr;T). In the EPI group, hemodynamics and respiration remained unchanged and only mild motor deficits occurred. &Dgr;T in thoracic segments was higher in the EPI than in the CON group (P < 0.001 at all times at high-thoracic, mid-thoracic, and low-thoracic segments). Skin temperature decreased in the distal tail in the EPI group, e.g., after 90 min &Dgr;T = −0.86 ± 0.25°C (EPI) versus 0.4 ± 0.12°C (CON) (P < 0.05 at 60, 90, and 120 min). &Dgr;T on day 3 was comparable to day 1. TEA induced stable segmental sympathetic block without cardiorespiratory and motor side effects in awake rats. This new technique may be applied in prolonged models of critical illness.

Intestinal effects of thoracic epidural anesthesia.

PURPOSE OF REVIEW Thoracic epidural anesthesia (TEA) is most frequently used after major surgery. However, despite ongoing research, the influence of TEA on the intestinal perioperative pathophysiology is not fully understood. RECENT FINDINGS According to recent results, the splanchnic sympathetic activity is reduced during TEA both in animal models and in clinical TEA. The splanchnic sympathetic activity during high TEA is still unknown. Intestinal perfusion effects of TEA are still unclear as the technique and extent of TEA, hemodynamic alteration and size of measurement result in--seemingly--conflicting reports. Postoperative ileus after laparotomy is ameliorated by TEA. Recent findings suggest beneficial effects also after major laparoscopic procedures. Finally, the impact of TEA on the intestinal pathophysiology in critical illness is an area of growing clinical and scientific interest, although this knowledge is just at its beginning. SUMMARY Further research concerning the use of TEA in major laparoscopic procedures and its potential to improve or endanger anastomotic healing is warranted. The experimental studies of TEA in critical illness should be expanded.