Biomedical subjects

Martin Welte

Publications and source records attributed to Martin Welte.

7 recordsLinked to original sources

PubMed2006

Influence of pain treatment by epidural fentanyl and bupivacaine on homing of opioid-containing leukocytes to surgical wounds.

Endogenous opioids released from leukocytes extravasating into injured tissue can interact with peripheral opioid receptors to inhibit nociception. Animal studies have shown that the homing of opioid-producing leukocytes to the injured site is modulated by spinal blockade of noxious input. This study investigated whether epidural analgesia (EDA) influences the migration of beta-endorphin (END) and/or met-enkephalin (ENK)-containing leukocytes into the subcutaneous wound tissue of patients undergoing abdominal surgery. In part I patients received general anesthesia combined either with intra- and postoperative EDA (with bupivacaine and fentanyl) or with postoperative patient controlled intravenous analgesia (PCIA; with the opioid piritramide). In part II patients received general anesthesia combined with either epidural fentanyl or bupivacaine which was continued postoperatively. Samples of cutanous and subcutanous tissue were taken from the wound site at the beginning, at the end and at various times after surgery, and were examined by immunohistochemistry for the presence of END and ENK. We found that (i) epidural bupivacaine, fentanyl and PCIA provided similar and clinically acceptable postoperative pain relief; (ii) compared to PCIA, epidural bupivacaine or fentanyl did not change the gross inflammatory reaction within the surgical wound; (iii) opioid-containing leukocytes were almost absent in normal subcutaneous tissue but migrated to the inflamed wound tissue in ascending numbers within a few hours, reaching a peak at about 24 h after surgery; (iv) compared to PCIA, EDA resulted in significantly decreased homing of END-containing leukocytes to the injured site at 24 h after surgery; and (v) the magnitude of this decrease was similar regardless of the epidural medication. These findings suggest that nociceptive but not sympathetic neurons are primarily involved in the attraction of opioid-containing leukocytes during early stages of inflammation.

Adjuvants, Anesthesia↗

PubMed2004

Effects of thoracic epidural anaesthesia on intestinal microvascular perfusion in a rodent model of normotensive endotoxaemia.

OBJECTIVE: To investigate whether sympathetic blockade by means of thoracic epidural anaesthesia (TEA) increases intestinal perfusion during normotensive endotoxaemia. DESIGN: A prospective, randomised and controlled animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Sprague-Dawley male rats. INTERVENTIONS: The rats were anaesthetised with urethane and ketamine, mechanically ventilated and haemodynamically monitored. Lidocaine or saline were infused continuously via thoracic epidural catheters followed by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (1.5 mg/kg per h). Densities of perfused and non-perfused capillaries (i.e., with and without erythrocyte perfusion, respectively) as well as erythrocyte velocity in both the mucosa and the muscularis of the terminal ileum were determined using intravital microscopy. MEASUREMENTS AND RESULTS: Measurements were performed at baseline, after 30 min of epidural infusion as well as after 60 and 120 min of lipopolysaccharide infusion. In animals receiving TEA, mean arterial pressure and heart rate were significantly reduced throughout the experiment. In the muscularis the endotoxaemia-induced increase in non-perfused capillaries was absent with epidural lidocaine (0 [0/0] versus 39 [36/137] cm(-1), median [25(th)/75(th) percentile]), whereas in the mucosa perfused capillary density declined to a greater extent than in controls (-47 [-53/-23]%) versus -19 [-34/+10]%, p<0.05). Erythrocyte velocity decreased with endotoxaemia and was not influenced by epidural lidocaine. CONCLUSIONS: Microvascular perfusion data during endotoxaemia show a redistribution of blood flow towards the mucosa. TEA seems to impede this redistribution resulting in improved muscularis and worsened mucosal microvascular perfusion.

Anesthesia, Epidural↗

PubMed2003

Modulation of peripheral endogenous opioid analgesia by central afferent blockade.

BACKGROUND: Peripheral tissue injury causes a migration of opioid peptide-containing immune cells to the inflamed site. The subsequent release and action of these peptides on opioid receptors localized on peripheral sensory nerve terminals causes endogenous analgesia. The spinal application of opioid drugs blocks the transmission of nociceptive information from peripheral injury. This study investigates the influence of exogenous spinal opioid analgesia on peripheral endogenous opioid analgesia. METHODS: Six and forty-eight hours after initiation of continuous intrathecal morphine infusion and administration of Freund's complete adjuvant into the hind paw of rats, antinociceptive and antiinflammatory effects were measured by paw pressure threshold, paw volume, and paw temperature, respectively. Inflammation and quantity of opioid-containing cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim stress-induced endogenous analgesia was examined 24 h after discontinuation of intrathecal morphine administration. RESULTS: Intrathecal morphine (10 micro g/h) resulted in a significant and stable increase of paw pressure threshold ( P< 0.05) without changing inflammation, as evaluated by paw volume, paw temperature, and flow cytometry ( P> 0.05). At 48 but not at 6 h after Freund's complete adjuvant, the number of beta-endorphin-containing cells and cold water swim-induced antinociception were significantly reduced in intrathecal morphine-treated rats compared with those treated with intrathecal vehicle ( P< 0.05). CONCLUSIONS: These findings suggest an interplay of central and peripheral mechanisms of pain control. An effective central inhibition of pain apparently signals a reduced need for recruitment of opioid-containing immune cells to injured sites.

Analgesics, Opioid↗

PubMed2003

Thoracic epidural anesthesia attenuates hemorrhage-induced impairment of intestinal perfusion in rats.

BACKGROUND: During hemorrhagic hypotension, sympathetic vasoconstriction crucially contributes to gut mucosal damage. Sympathetic blockade by thoracic epidural anesthesia has been shown to increase mucosal microvascular perfusion and to improve survival after severe hemorrhage in laboratory animals. This study investigates the effects of thoracic epidural anesthesia on intestinal microvascular perfusion during hemorrhagic hypotension in rats. METHODS: In 32 anesthetized Sprague-Dawley rats either lidocaine 2% (thoracic epidural anesthesia) or normal saline (control) was infused via thoracic epidural catheters. Hemorrhagic hypotension (mean arterial pressure 30 mmHg for 60 min) was induced by withdrawal of blood, which was subsequently retransfused for resuscitation. Functional capillary density and erythrocyte velocity in the mucosa and muscularis were determined by intravital microscopy. Leukocyte-endothelium interaction was studied in postcapillary venules and sympathetic nerve fibers of the intestinal wall were identified by immunohistochemistry. RESULTS: During hypotension functional capillary density was significantly (P < 0.001) lower in the muscularis of the control group (median [25/75 percentile]: -46.5% [-59.6/-20.8%] change from baseline) as compared with animals that received thoracic epidural anesthesia (-6.1% [-13.4/1.1%]). There were no differences in erythrocyte velocity between groups throughout the experiment. Leukocyte rolling increased significantly (P < 0.001) after resuscitation in control (12 [6/15] vs. baseline 2.5 [1/8]) but not in thoracic epidural anesthesia (4 [2.3/7] vs. baseline: 5 [3/15.5]). Sympathetic nerve fibers were identified in the muscularis and submucosa but not in the mucosa. CONCLUSIONS: During hemorrhagic hypotension and after resuscitation, thoracic epidural anesthesia has beneficial effects on intestinal microvascular perfusion. Because of blockade of sympathetic nerves, thoracic epidural anesthesia prevents perfusion impairment of the muscularis during hypotension and attenuates leukocyte rolling after resuscitation.

Acid-Base Equilibrium↗

PubMed2002

Use of perflubron emulsion to decrease allogeneic blood transfusion in high-blood-loss non-cardiac surgery: results of a European phase 3 study.

BACKGROUND: This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care. METHODS: Subjects (N = 492) with hemoglobin concentrations of 12-15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 +/- 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 +/- 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 +/- 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 +/- 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 +/- 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion. RESULTS: Both groups had similar hemoglobin concentrations at screening (13.5 +/- 1.0 g/dl) and at discharge: 10.8 +/- 1.2 g/dl (PFC) and 11.1 +/- 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53% vs. 43%, < 0.05), and fewer erythrocytes were transfused (1.5 +/- 4.8 vs. 2.1 +/- 3.9 units; median, 0 vs. 1 unit; P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss > or = 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26% vs. 16% in the PFC and control groups, respectively; P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 +/- 2.9 vs. 4.9 +/- 2.4 units; median 2 vs. 4 units; P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%; P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4% vs. controls, 2%) was not statistically significant. CONCLUSIONS: Augmented acute normovolemic hemodilution with PFC reduces transfusion needs in patients undergoing noncardiac surgical procedures with blood loss 20 ml/kg or greater.

Adult↗

PubMed2002

Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebo-controlled phase II study.

OBJECTIVE: To compare dexmedetomidine vs. placebo with respect to the amount of additional propofol and morphine used for bispectral index-guided sedation and analgesia in mechanically ventilated, intensive care patients after surgery. DESIGN: Prospective, randomized, double blind, placebo-controlled, phase II clinical trial. SETTING: General surgical and cardiac surgical intensive care units. PATIENTS: Thirty patients scheduled for major surgery requiring mechanical ventilation for a minimum of 6 hrs were included in the study. INTERVENTIONS: Patients were assigned randomly to receive either dexmedetomidine (loading infusion, 6.0 microg x kg(-1) x hr(-1) for 10 mins; maintenance infusion, 0.1-0.7 microg x kg(-1) x hr(-1)) or placebo after intensive care unit admission. MEASUREMENTS AND MAIN RESULTS: Sedation was guided by using the electroencephalographic parameter bispectral index, a new noninvasive method to estimate the level of sedation. We aimed at maintaining bispectral index ranges between 60 and 70 during mechanical ventilation before starting weaning, 65 and 95 during weaning, and 85 to 95 postextubation. Additional sedative and analgesic medication was given (propofol and morphine) as clinically indicated and within the previously mentioned bispectral index ranges. Patients receiving dexmedetomidine required significantly less propofol during mechanical ventilation (0.87 +/- 0.21 vs. 1.52 +/- 0.30 mg x kg(-1) x hr(-1); p <.01) and weaning (0.17 +/- 0.06 vs. 0.62 +/- 0.21 mg x kg(-1) x hr(-1); p <.001) to maintain the target bispectral index range. During study drug administration, morphine requirements for dexmedetomidine-treated patients were reduced by 58% (p =.05). Hemodynamic stability during weaning and after extubation was better maintained in patients receiving dexmedetomidine. CONCLUSIONS: Dexmedetomidine reduced propofol requirements and improved hemodynamic stability during bispectral index-guided intensive care unit sedation.

Adrenergic alpha-Agonists↗

PubMed2002

Effects of hypothermia on median nerve somatosensory evoked potentials during spontaneous circulation.

Perioperative-induced hypothermia is a common means of reducing ischemic injury in neurosurgical procedures and cardiac surgery, and it may occur accidentally. Somatosensory evoked potentials (SSEPs) are used frequently for neurophysiologic monitoring of these procedures. The effects of hypothermia on SSEPs have been studied widely in humans with cardiopulmonary bypass (CPB) during nonpulsatile flow. However, changes of latency and amplitude of early SSEP components during spontaneous circulation have not yet been studied. Median nerve SSEPs were recorded in 21 patients during rewarming from 32 to 36 degrees C core temperature. Latencies and amplitudes of N9, N13, N20, and central conduction time were registered at 32, 34, and 36 degrees C. Latencies of N9, N13, and N20 were prolonged at 32 degrees C compared with 36 degrees C (N9: 13.4 +/- 1.4 msec versus 11.8 +/- 1.4 msec, P <.05; N13: 17.6 +/- 1.9 msec versus 15.4 +/- 1.4 msec, P <.01; N20: 26.5 +/- 1.8 msec versus 22.4 +/- 1.6 msec, P <.001). Amplitude of N20 was higher at 32 degrees C compared with 36 degrees C (2.86 +/- 1.94 microV versus 2.07 +/- 1.47 microV, P < .05). Central conduction time decreased by 27%, and peripheral latency of N13 decreased by 14%. The increase in SSEP latency (N9, N13, and N20) and central conduction time during moderate hypothermia of 32 degrees C and spontaneous circulation are comparable with those during nonpulsatile flow on CPB. In contrast to nonpulsatile flow, the amplitude of N20 was increased significantly (P < .05) during moderate hypothermia and pulsatile circulation. These results suggest to be cautious about generalizing the effects of hypothermia on SSEP during CPB to spontaneous circulation.

Adult↗