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Biomedical subjects

M Licker

Publications and source records attributed to M Licker.

At least 55 records · Page 3Linked to original sources

Inhibitors of the renin angiotensin system: implications for the anaesthesiologist.

The major long-term benefits of angiotensin-converting enzyme (ACE) inhibitors have now clearly been demonstrated in patients with arterial hypertension, cardiac insufficiency, coronary artery disease and several renal diseases. Such long-term treatment markedly alters the cardiovascular response to anaesthesia and surgery, whereas preliminary data suggest that short-term renin angiotensin system blockade might provide perioperative organ protection and improved circulatory conditions. Besides the classic view that the conversion of angiotensin I to angiotensin II is mainly due to ACE, alternative pathways have recently been identified, including cathepsin G as well as chymostatin- and aprotinin-sensitive serine proteases that are released from mastocytes and endothelial cells and which are insensitive to the effects of ACE inhibitors. These proteases are thought to contribute to tissue perfusion under hypoxic conditions and to structural remodelling. In clinical practice, ACE inhibitors may be preferred to angiotensin II receptor antagonists since the former, besides reducing angiotensin II synthesis, also lead to an accumulation of kinins (e.g. bradykinin), which have important cardio- and renal protective effects through liberation of prostacyclin and nitric oxide in endothelial cells and through stimulation of guanylate cyclase to form cyclic GMP.

Journal Article↗

Haemodynamic and metabolic changes induced by repeated episodes of hypoxia in pigs.

BACKGROUND: Repeated hypoxia and surgical trauma trigger a potent neuroendocrine response and their association is thought to play a pivotal role in the pathogenesis of multi-organ dysfunction. We investigated the cardiovascular and metabolic responses to repeated acute hypoxia in anaesthetised and surgically instrumented pigs. METHODS: Under ketamine-midazolam anaesthesia, 15 pigs were surgically instrumented for measurements of cardiac output, vascular pressures and organ blood flows. Lactate production and O2 uptake were determined in the brain, liver, kidney and intestine. Ten animals were subjected to two 12-min periods of ventilatory hypoxia (FIO2 = 7%) followed by re-oxygenation and 5 animals underwent 120-min normoxic ventilation (Control group). RESULTS: Both hypoxic challenges produced a comparable release of catecholamines that was associated with increased cardiac output and redistribution of blood flow away from the intestinal and renal areas towards the brain and the liver; O2 uptake was markedly reduced in the intestine (-56 +/- 10%, P < 0.05) and least affected in the brain and the kidney (-19 +/- 12% and -23 +/- 21%, respectively). During the second hypoxic test, lethal cardiovascular depression occurred in 5 animals; these non-survivors demonstrated impaired hyperdynamic response and incomplete recovery of intestinal O2 uptake during the first hypoxia/reoxygenation test. In the Control group, normoxic ventilation was not associated with significant haemodynamic and metabolic changes. CONCLUSION: Intraoperative hypoxia causes marked heterogeneity in organ blood flow and metabolism. The inability to develop a hyperdynamic cardiovascular response during a first hypoxic event, as well as a persistent intestinal O2 debt following re-oxygenation, predict the occurrence of death during the second hypoxic insult.

Anesthesia↗

Successful combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas.

Pulmonary lymphangioleiomyomatosis (LAM) and renal angiolipomas are rare but distinct clinical entities that share similar morphological features. Lung transplantation is considered as a valuable therapeutic modality in patients with end-stage pulmonary LAM. However, in some patients, renal complications due to bleeding angiomyolipomas and cyclosporin-induced nephropathy have become newly identified problems. This study reports the first case of combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas. Two years after transplantation, renal and pulmonary function have remained stable and the patient has resumed a normal daily life, including a full-time professional activity.

Adult↗

Thermoregulatory and metabolic responses following cardiac surgery.

The thermoregulatory responses in 13 haemodynamically stable patients were evaluated over a 7-h period following coronary artery bypass graft surgery. Cutaneous vasoconstriction was defined by a forearm-to-fingertip skin temperature gradient (delta Tskin) > or = 4 degrees C and muscular hyperactivity was assessed by integrating the electromyographic signals (iEMG). Blood gases and lactate were measured in arterial, mixed venous and femoral venous blood. After arrival in ICU, we observed: (1) mild central hypothermia (Tc = 34.8 +/- 0.6 degrees C) and elevated peripheral vascular resistance in all the patients; (2) delta Tskin > or = 4 degrees C in 11 of 13 patients that persisted until a median Tc of 37.1 degrees C was achieved; (3) a transient increase in iEMG (+ 18%) was accompanied by an increase in total body O2 uptake (+ 28%); (4) elevated muscle O2 extraction rate (56 +/- 18% after 3 h) and lactate release. These data suggest that residual hypothermia in sedated patients after cardiac surgery elicits appropriate thermoregulatory responses that are associated with transient O2 supply/uptake mismatch within skeletal muscles.

Acid-Base Equilibrium↗

Relation between systemic oxygen uptake and tissue oxygen extraction following cardiac surgery.

Twenty-three patients undergoing elective coronary artery bypass graft surgery with moderate hypothermic bypass, under opiate-benzodiazepine anaesthesia were investigated during the first 7 h following surgery. Patients with recent myocardial infarct (< 6 weeks), reduced left ventricular ejection fraction (< 40%) or requiring inotropic support were excluded. During the first 3 h after surgery, higher oxygen uptake and oxygen extraction ratio were found in shivering patients (n = 5) compared with non-shivering patients (N = 16). A significant relation was found between oxygen uptake and the oxygen extraction ratio for the pooled data (R = 0.80 and 0.87, in shivering and non-shivering patients, respectively) as well as for the individual patients. A weaker relation was observed between cardiac output and oxygen uptake. The lack of adequate circulatory compensation could be related to the myocardium, surgical trauma, cardioplegic arrest and to peripheral vasoconstriction.

Anesthesia, General↗

Preoperative inhibition of angiotensin-converting enzyme improves systemic and renal haemodynamic changes during aortic abdominal surgery.

We studied 22 patients undergoing aortic surgery, allocated randomly to receive, before induction of anaesthesia, a single i.v. dose of enalapril 50 micrograms kg-1 or saline. During infrarenal aortic cross-clamping, we observed similar reductions in oxygen uptake in the two groups, despite greater systemic oxygen delivery in enalapril-treated patients; angiotensin-converting enzyme inhibition prevented the reduction in cardiac output and attenuated the decrease in glomerular filtration. Changes in glomerular filtration secondary to aortic clamping were related positively to changes in renal plasma flow (r = 0.83 (saline group) and r = 0.65 (enalapril group)). Creatinine clearance on the first day after operation was significantly higher in the enalapril compared with the saline group. We conclude that enalapril pretreatment is effective in improving systemic oxygen delivery, renal plasma flow and glomerular filtration during aortic abdominal surgery.

Aged↗

Long-term angiotensin-converting enzyme inhibitor treatment attenuates adrenergic responsiveness without altering hemodynamic control in patients undergoing cardiac surgery.

BACKGROUND: The sympathoadrenal and the renin-angiotensin systems are involved in blood pressure regulation and are known to be markedly activated during cardiac surgery. Because unexpected hypotensive events have been reported repeatedly during anesthesia in patients chronically treated with angiotensin-converting enzyme (ACE) inhibitors, the authors questioned whether renin-angiotensin system blockade would alter the hemodynamic control through attenuation of the endocrine response to surgery and/or through attenuation of the pressor effects of exogenous catecholamines. METHODS: Patients with preserved left ventricular function undergoing mitral valve replacement or coronary revascularization were divided into two groups according to preoperative drug therapy: patients receiving ACE inhibitors for at least 3 months (ACEI) group, n = 22) and those receiving other cardiovascular drug therapy (control group, n = 19). Anesthesia was induced using fentanyl and midazolam. Systemic hemodynamic variables were recorded before surgery, after anesthesia induction, during sternotomy, after aortic cross-clamping, after aortic unclamping, as well as after separation from cardiopulmonary bypass (CPB) and during skin closure. Blood was sampled repeatedly up to 24 h after surgery for hormone analysis. To test adrenergic responsiveness, incremental doses of norepinephrine were infused intravenously during hypothermic CPB and after separation from CPB. From the dose-response curves, pressor (defined as mean arterial pressure changes), and vasoconstrictor (defined as systemic vascular resistance changes) effects were analyzed, and the slopes and the dose of norepinephrine required to increase mean arterial pressure by 20% were calculated (PD(20)). RESULTS: At no time did the systemic hemodynamics and the need for vasopressor support differ between the two treatment groups. However, for anesthesia induction, significantly less fentanyl and midazolam were given in the ACEI group. Although plasma renin activity was significantly greater in the ACEI group throughout the whole 24-h study period, plasma concentrations of angiotensin II did not differ between the two groups. Similar changes in catecholamines angiotensin II, and plasma renin activity were found in the two groups in response to surgery and CPB. The pressor and constrictor effects of norepinephrine infusion were attenuated markedly in the ACEI group: the dose-response curves were shifted to the right and the slopes were decreased at the two study periods; PD(20) was significantly greater during hypothermic CPB (0.08 micro/kg in the ACEI group vs. 0.03 micro/kg in the control group; P < 0.05) and after separation from CPB (0.52 micro/kg in the ACEI group vs. 0.1 micro/kg in the control group; P < 0.05). In both groups, PD(20) was significantly less during hypothermic CPB than in the period immediately after CPB. CONCLUSIONS: Long-term ACE inhibitor treatment in patients with preserved left ventricular function alters neither the endocrine response nor the hemodynamic stability during cardiac surgery. However, a significantly attenuated adrenergic responsiveness associated with incomplete blockade of the plasma renin-angiotensin system supports the hypothesis that inhibition of angiotensin II generation and of bradykinin degradation within the vascular wall mediates some of the vasodilatory effects of ACE inhibitors.

Adult↗

Cardiovascular reflexes during anesthesia induction and tracheal intubation in elderly patients: the influence of thoracic epidural anesthesia.

STUDY OBJECTIVES: To determine whether thoracic epidural anesthesia performed prior to general anesthesia provides hemodynamic protection from the stress of laryngoscopy and tracheal intubation; to access the autonomic reflex response to epidural anesthesia, general anesthesia, and airway stimulation. DESIGN: Randomized unblind, controlled study. PATIENTS AND SETTING: 20 elderly (over 60) patients scheduled for colonic or gastric surgery at a university medical center. INTERVENTIONS: All patients (n = 10, in each group) underwent a standardized anesthesia induction sequence that included fentanyl 2 micrograms/kg, thiopental sodium 3 to 5 mg/kg (up to loss of eyelid reflex), and vecuronium 0.1 mg/kg followed by laryngoscopy and tracheal intubation. Before general anesthesia, thoracic epidural anesthesia was performed with plain 1% lidocaine in the epidural group. Preoperatively, baroreflex function was assessed by the Valsalva maneuver and the cough test. Spectral analysis of heart rate (HR) variability was performed before as well as during anesthesia. MEASUREMENTS AND MAIN RESULTS: There were no differences between the two groups in basal hemodynamics autonomic reflex status. Thoracic epidural anesthesia (median upper level at T2, median lower level at L2) was associated with stable hemodynamics, preservation of baroreflex sensitivity, and increased ratio of low to high frequency (LF/HF) components of HR variability, suggesting withdrawal of vagal activity. In both groups, general anesthesia induction was associated with decreased total HR variability and tracheal intubation was followed by increased LF/HF ratio, reflecting cardiac sympathetic activation. Patients with thoracic epidural anesthesia presented significant attenuation of the maximal rise in mean arterial pressure, and the increase in HR tended to be lower although not significantly. CONCLUSIONS: Thoracic epidural blockade combined with general anesthesia was associated with preserved baroreflex function, and it afforded hemodynamic protection during laryngoscopy and tracheal intubation.

Aged↗

Metabolic response to lower abdominal surgery: analgesia by epidural blockade compared with intravenous opiate infusion.

To determine whether the type of peri-operative analgesic regimen affects the metabolic response during and after surgery, we studied 19 women undergoing abdominal hysterectomy under propofol anaesthesia. Patients were randomized to receive either continuous intravenous opioid or a bupivacaine-opioid mixture through a lumbar epidural catheter. Total body oxygen consumption and carbon dioxide excretion, blood glucose and haemodynamic variables were determined up to 24 h after surgery. No differences in any metabolic or haemodynamic variables were noted during surgery. In the post-operative period, the increase in oxygen consumption up to pre-operative values, the urinary nitrogen excretion and the changes in acute phase proteins were similar in both treatment groups. In contrast, the respiratory quotient was significantly higher in the lumbar epidural group than in the intravenous opioid group, 0.87 (SD 0.04) vs 0.77 (SD 0.06) (P < 0.05) and the hyperglycaemic response was more delayed in the epidural group. These data suggest that prolonged sympathetic blockade associated with epidural analgesia might contribute to better preservation of glucose homeostasis in the perioperative period.

Acute-Phase Proteins↗