[Change in therapy target and therapy limitations in intensive care medicine. Position paper of the Ethics Section of the German Interdisciplinary Association for Intensive Care and Emergency Medicine]. / Therapiezieländerung und therapiebegrenzung in der intensivmedizin. Positionspapier der Sektion Ethik der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin.

The task of physicians is to maintain life, to protect and re-establish health as well as to alleviate suffering and to accompany the dying until death, under consideration of the self-determination rights of patients. Increasingly more and differentiated options for this are becoming available in intensive care medicine. Within the framework of professional responsibility physicians must decide which of the available treatment options are indicated. This process of decision-making is determined by answering the following question: when and under which circumstances is induction or continuation of intensive care treatment justified? In addition to the indications, the advance directive of the patient is the deciding factor. Medical indications represent a scientifically based estimation that a therapeutic measure is suitable in order to achieve a defined therapy target with a given probability. The ascertainment of the patient directive is achieved in a graded process depending on the state of consciousness of the patient. The present article offers orientation assistance to physicians for these decisions which are an individual responsibility.

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer.

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.

Propofol concentration in exhaled air and arterial plasma in mechanically ventilated patients undergoing cardiac surgery.

BACKGROUND: Measuring propofol concentration in plasma (c(P)PL) and in exhaled alveolar gas (c(P)G) during constant infusion provides information about their respective time courses. In the present study, we compared these time courses in patients undergoing cardiac surgery from the beginning of propofol anaesthesia until eye opening upon awakening. METHODS: The c(P)G was measured before, during, and after continuous infusion of propofol for general anaesthesia in 12 patients at two randomly allocated doses (3 or 6 mg kg(-1) h(-1)). Gas samples were collected on Tenax tubes. After thermodesorption, c(P)G was measured by gas chromatography mass spectrometry. Simultaneously with exhaled gas, arterial blood was sampled for measuring c(P)PL by reversed-phase high-performance liquid chromatography with fluorescence detection. In order to compare the time courses of c(P)PL and c(P)G as dimensionless values directly, each gas and plasma value was normalized by relating it to the corresponding value at the end of the initial infusion after 40 min. RESULTS: The c(P)G ranged between 2.8 and 22.5 ppb, whereas the corresponding c(P)PL varied between 0.3 and 3.3 microg ml(-1). Normalized concentration values showed a delayed increase in c(P)G compared with c(P)PL under constant propofol infusion before the onset of cardiopulmonary bypass, and a delayed decrease after stopping the propofol at the end of anaesthesia. CONCLUSIONS: Propofol can be measured in exhaled gas from the beginning until the end of propofol anaesthesia. The different time courses of c(P)PL and c(P)G have to be considered when interpreting c(P)G.

Blood gas partition coefficient and pulmonary extraction ratio for propofol in goats and pigs.

The interpretation of continuously measured propofol concentration in respiratory gas demands knowledge about the blood gas partition coefficient and pulmonary extraction ratio for propofol. In the present investigation we compared both variables for propofol between goats and pigs during a propofol anaesthesia. In ten goats and ten pigs, expired alveolar gas and arterial and mixed venous blood samples were simultaneously drawn during total intravenous anaesthesia with propofol. The blood gas partition coefficient and pulmonary extraction ratio were calculated for both species. Non-parametric methods were used for statistical inference. The blood gas partition coefficient ranged between 7000 and 646,000 for goats and between 17,000 and 267,000 for pigs. The pulmonary extraction ratio ranged between 32.9% and 98.1% for goats and was higher for pigs, which ranged between -106.0% and 39.0%. The blood gas partition coefficient for propofol exceeded those for other known anaesthetic compounds so that it takes longer to develop a steady-state. The different pulmonary extraction rates in two species suggest that there are different ways to distribute propofol during the lung passage on its way from the blood to breathing gas. This species-specific difference has to be considered for methods using the alveolar gas for monitoring the propofol concentration in plasma.

[Psychological traits, course of surgery and recovery following hernia repair in patients preferring general or local anaesthesia]. / Psychologische Persönlichkeitsmerkmale, Operationsverlauf und Genesung bei Patienten mit Präferenz für Allgemein- oder Lokalanästhesie: Untersuchung an Patienten mit Leistenhernienoperation.

OBJECTIVE: This study addresses two questions concerning open inguinal hernia repair patients: (1) are there differences in psychological traits between patients opting for local vs. general anaesthesia and (2) assuming comparable operations, are there any differences between the two groups during surgery and postoperative recovery? METHODS: A total of 69 male patients aged between 18 and 80 took part in the study. After having been briefed about anaesthesia, they opted for either local (n=40) or general anaesthesia (n=29). In order to determine psychological traits, patients filled out questionnaires before the operation [NEO Five-Factor-Inventory (NEO-FFI) and the Stress Coping Questionnaire (SVF)] and the Anaesthesiological Questionnaire (ANP) after the operation. Data about the surgery (duration of anaesthesia and operation, blood pressure and heart rate) and the convalescence period (time spent in recovery room, length of stay in hospital) were also recorded. The patients' information processing skills were measured preoperatively and postoperatively using the "Trail Making Test". RESULTS: Patients preferring local anaesthesia were significantly older than those who chose general anaesthesia. Therefore two similar age groups were formed by using the method of matched samples (n=2x26). Between these groups no significant differences were found with reference to psychological traits, but markedly extraverted patients favoured local anaesthesia. There were no differences in the duration of anaesthesia and surgery. Local anaesthesia patients spent less time in the recovery room and in hospital than general anaesthesia patients. Postoperatively, the cognitive state and the satisfaction with the anaesthesia were comparable between both groups. CONCLUSION: Psychological traits do not have a significant impact on the choice of either local or general anaesthesia. However, highly extraverted patients prefer local anaesthesia while extreme introverts prefer general anaesthesia. Our findings suggest that local anaesthesia will become more widely adopted for the repair of groin hernia. Future studies should focus on optimising the perioperative care for patients who choose local anaesthesia.

Ifosfamide and carboplatin combined with 41.8 degrees C whole-body hyperthermia in patients with refractory sarcoma and malignant teratoma.

The purpose of this study was to evaluate the pharmacokinetics, biological interactions, and toxicities of ifosfamide and carboplatin combined with 41.8 degrees C whole-body hyperthermia (WBH) for 1 h in a pilot clinical study. Nineteen patients with refractory sarcoma or malignant teratoma were treated. To obtain baseline pharmacokinetic data for ifosfamide, the first chemotherapy course was given without WBH in six patients. This enabled comparison of systemic toxicity and pharmacokinetics of the drug combination with and without WBH (+/- WBH). All other patients received three thermochemotherapy treatments every 3 weeks. Ifosfamide was escalated from 5 to 10 g/m2 with a fixed carboplatin dose of 480 mg/m2. WBH was induced by extracorporally heated blood (in a hemodialysis apparatus) with general anesthesia. The drugs were given at target temperature. A total of 49 thermochemotherapy treatments was administered. The use of the hemodialysis device resulted in an approximate one-third reduction of blood concentrations of 4-hydroxyifosfamide, one activated intermediate metabolite of ifosfamide and carboplatin, but in an increase of chloroacetaldehyde, the other main ifosfamide metabolite. The WBC counts and the platelet nadirs (up to WBH grade 4) were not significantly different +/- WBH. Of 19 evaluable patients, 7 partial remissions, 8 disease stabilizations (average duration, 3 months), and 4 patients with progressive disease were observed. There was no WBH-related mortality. Toxicities observed included mild (anasarca, diarrhea, pressure sores, and perioral herpes simplex) and severe (reversible neuropathy, cardiopulmonary distress, and severe renal dysfunction). No hepatic or central nervous system toxicity occurred. Nephropathy was the dose-limiting toxicity. In conclusion, ifosfamide and carboplatin can be administered with extracorporally induced WBH with acceptable toxicity. Results obtained are consistent with continued evaluation of this combined modality approach.

Upregulation of IFN-gamma and soluble interleukin-2 receptor release and altered serum cortisol and prolactin concentration during general anesthesia.

The effects of surgery, surgical stress, and anesthesia compromise the optimal function of the immune system. Recent studies demonstrate the influence of anesthesia on the immune response by modulation of neural-immune interactions. To evaluate the immunologic effects of general anesthesia with the hypnotic agent propofol and the opioid fentanyl, two drugs used frequently in anesthesia, we studied 30 patients undergoing elective orthopedic surgery before and during narcosis. We found a significant enhancement of interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor (sIL-2R) release in lipopolysaccharide (LPS)-stimulated whole blood cultures after induction of anesthesia. Similar results were observed in cultures stimulated with polyclonal T cell activators, such as staphylococcal enterotoxin B (SEB) and phytohemagglutinin (PHA). IL-1beta and IL-8 release was not affected, but the anti-inflammatory cytokine IL-10 decreased after skin incision. Serum prolactin significantly increased immediately after induction of anesthesia, whereas serum cortisol levels declined. Our results point to enhanced proinflammatory T lymphocyte and natural killer (NK) cell activity, probably caused by prolactin and cortisol modulation in the serum. This may disturb the balance of human proinflammatory and anti-inflammatory pathways during surgery and general anesthesia.

The immune-endocrine interaction varies with the duration of the inflammatory process in cardiac surgery patients.

The present study investigated the perioperative course of cytokine release and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to the duration of the inflammatory response in cardiac surgery patients. Twelve male patients scheduled for elective coronary artery bypass grafting surgery with cardiopulmonary bypass and general anaesthesia were divided into two study groups: group 1 (n=6) underwent surgery at 13.00 h+/-30 min, group 2 (n=6) at 08.30 h+/-50 min. Blood samples were collected preoperatively and up to the first postoperative day. Postoperatively, on the day of surgery, serum concentrations of the proinflammatory cytokines interleukin (IL)-6, IL-1beta and tumour necrosis factor (TNF)-alpha were not significantly different between the two groups, while blood concentrations of cortisol, adrenocorticotrophic hormone (ACTH) and beta-endorphin in group 2 patients were significantly higher than in group 1 patients. Postoperatively, on the day of surgery, ACTH and cortisol concentrations in group 1 patients were positively correlated to the blood concentrations of IL-1beta, IL-6 and TNF-alpha. By contrast, group 2 patients showed no significant relationship between cytokine release and activation of HPA axis at this time. Our results suggest that in patients undergoing cardiac surgery, the cytokine response is initiated before the HPA axis is fully activated. In the early postoperative period, cytokines appear to be involved in the activation of the HPA axis, while in the later postoperative period, high cortisol concentrations may inhibit the release of IL-6.

Treatment of acute left heart failure using dobutamine and intraaortic counterpulsation. Animal experiments and first clinical experiences.

Ten anesthetized mongrel dogs had a left anterolateral thoracotomy; the left anterior descending coronary artery was then ligated. After 60 min five animals each were treated either with dobutamine (4 microgram/min/kg; for 10 min), or with dobutamine and intraaortic counterpulsation. Combined treatment of cardiogenic shock proved superior. Those five dogs had significantly lower heart rates and dp/dt/p-values. Due to IABP the non-ischemic parts of the left ventricle were better perfused; there was no difference in treatment with regard to ischemic parts. The combined treatment was successfully inaugurated in two patients with cardiogenic shock.

Early postoperative thrombolytic therapy after laparotomy.

Early postoperative pulmonary embolism due to deep venous thrombosis has been reported to be associated with a mortality rate of approximately 46%. Administration of thrombolytic drugs is relatively contraindicated during this period so that conservative or surgical treatment can be considered as a therapeutical intervention. We report the case of a 68-year-old male patient who was subjected to systemic thrombolytic therapy due to pulmonary embolism on the first day after laparatomy.

Optimisation of tidal volumes given with self-inflatable bags without additional oxygen.

The European Resuscitation Council has recommended smaller tidal volumes of 500 ml during basic life support ventilation in order to minimise gastric inflation. One method of delivering these tidal volumes may be to use paediatric instead of adult self-inflatable bags; however, we have demonstrated in other studies that only 350 ml may be delivered, using this technique. The reduced risk of gastric inflation was offset by oxygenation problems, rendering the strategy of attempting to deliver tidal volumes of 500 ml with a paediatric self-inflatable bag questionable, at least when using room-air. In this report, we assessed the effects of a self-inflatable bag with a size between the maximum size of a paediatric (700 ml) and an adult (1500 ml) self-inflatable bag on respiratory variables and blood gases during bag-valve-mask ventilation. After induction of anaesthesia, 50 patients were block-randomised into two groups of 25 each. They were ventilated with room-air with either an adult (maximum volume, 1500 ml) or a newly developed medium-size (maximum volume, 1100 ml; Dräger, Lübeck, Germany) self-inflatable bag for 5 min before intubation. When compared with the adult self-inflatable bag, the medium-size bag resulted in significantly lower exhaled tidal volumes and tidal volumes per kg bodyweight (624 + 24 versus 738 +/- 20 ml, and 8.5 +/- 0.3 versus 10.7 +/- 0.3 ml kg(-1), respectively; P < 0.001), oxygen saturation (95 +/- 0.4 versus 96 +/- 0.3%; P < 0.05), and partial pressure of oxygen (78 +/- 3 versus 87 +/- 3 mmHg; P < 0.05). Carbon dioxide levels were comparable (37 +/- 1 versus 37 +/- 1 mmHg). Our results indicate that smaller tidal volumes of about 8 ml x kg(-1) (approximately 600 ml), given with a new medium-size self-inflatable bag and room-air, maintained adequate carbon dioxide elimination and oxygenation during bag-valve-mask ventilation. Accordingly, the new medium-size self-inflatable bag may combine both adequate ventilatory support and reduced risk of gastric inflation during bag-valve-mask ventilation.

Smaller tidal volumes during cardiopulmonary resuscitation: comparison of adult and paediatric self-inflatable bags with three different ventilatory devices.

Gastric inflation and subsequent regurgitation of stomach contents is a major hazard of bag-valve-face mask ventilation during the basic life support phase of cardiopulmonary resuscitation (CPR). Recent investigations suggested that use of a paediatric self-inflating bag may reduce stomach inflation while ensuring sufficient lung ventilation. The purpose of our study was to examine whether use of a paediatric self-inflating bag in association with laryngeal mask airway, combitube, and bag-valve-face mask may provide adequate lung ventilation, while reducing the risk of gastric inflation in a bench model simulating the initial phase of CPR. Sixteen intensive care unit registered nurses volunteered for our study. Use of a paediatric versus adult self-inflating bag resulted in a significantly (P < 0.01) lower mean (+/- S.D.) tidal lung volume with both the laryngeal mask airway and combitube (laryngeal mask airway 349 +/- 149 ml versus 725 +/- 266 ml, combitube 389 +/- 113 ml versus 1061 +/- 451 ml). Lung tidal volumes were below the European Resuscitation Council recommendation with both self-inflatable bags in the bag-valve-face mask group (paediatric versus adult self-inflatable bag 256 +/- 77 ml versus 334 +/- 125 ml). Esophageal tidal volumes were significantly (P < 0.05) lower using the paediatric self-inflatable bag in the bag-valve-face mask group; almost no gastric inflation occurred with the laryngeal mask airway, and none with the combitube. In conclusion, use of the paediatric self-inflating bag may reduce gastric inflation, but measured lung tidal volumes are below the European Resuscitation Council recommendation when used with either, the laryngeal mask airway, combitube, or bag-valve-face mask.

Airway management during cardiopulmonary resuscitation--a comparative study of bag-valve-mask, laryngeal mask airway and combitube in a bench model.

Gastric inflation and subsequent regurgitation are a potential risk of ventilation during cardiopulmonary resuscitation (CPR). In respect of recent investigations, principal respiratory components such as respiratory system compliance, resistance and lower esophageal sphincter pressure were adapted according to CPR situations. The purpose of our study was to assess lung ventilation and gastric inflation when performing ventilation with bag-valve-mask, laryngeal mask airway, and combitube in a bench model simulating an unintubated cardiac arrest patient. Twenty-one student nurses, without any experience in basic life support measures, ventilated the bench model with all three devices. Mean ( +/- S.D.) gastric inflation with the laryngeal mask airway (seven cases) was significantly lower than with the bag-valve-mask (0.6 +/- 0.8 vs 3.0 +/- 2.11 min(-1), P < 0.01). There was no gastric inflation when ventilation was performed with the combitube. Only seven of 21 volunteers exceeded 1-min lung volumes of > 5 1 when using the bag-valve-mask, whereas mean (+/-S.D.) 1-min lung volumes with both laryngeal mask airway and combitube were significantly higher (laryngeal mask airway 15.0+/-6.61, combitube 16.6 +/- 6.81 vs bag-valve-mask 4.8 +/- 2.71, P < 0.01). The time for insertion was significantly faster with both bag-valve-mask and laryngeal mask airway compared with the combitube (median: bag valve mask 22 s, laryngeal mask airway 37 s vs combitube 70 s, P < 0.01). This may tip the scales towards using the laryngeal mask airway during basic life support airway management. In conclusion, our data suggests that both laryngeal mask airway and combitube may be appropriate alternatives for airway management in the first few minutes of CPR.

Pentoxifylline improves circulatory and metabolic recovery after cardiopulmonary resuscitation.

BACKGROUND: To evaluate the effectiveness of a bolus application of pentoxifylline (PTXF) at the beginning of CPR in a standardized resuscitation animal model. METHODS AND RESULTS: In a laboratory model of cardiac arrest, 12 Wistar rats (382-413 g) were randomized into two groups. Both groups underwent 4 min of cardiopulmonary arrest induced by a transthoracic application of a fibrillating current of 10 mA. At the beginning of CPR, group one (n=6) received a bolus injection of 10 mg kg(-1) body weight PTXF versus sodium chloride in group two (controls: n=6). All animals developed a severe lactate acidosis during and after CPR but in PTXF treated animals acid-base values returned to baseline pattern. During return of spontaneous circulation (ROSC) in the PTXF group lactate concentration decreased from 13.4+/-2.1 to 1.9+/-0.7 mmol l(-1) within 60 min (P<0.01). In control animals, lactate values remained high (10.8+/-3.5 by 60 min, P<0.01). After bolus injection of PTXF pH increased from 6.93+/-0.06 to 7.29+/-0.13 within 60 min of ROSC versus 6.85+/-0.05 to 6.97+/-0.23 in sodium chloride treated animals (P<0.01). Within 5 min of ROSC, PTXF treated animals achieved higher oxygenation values (PTXF P(a)O(2)=216.9+/-62.5 mmHg, control 132. 2+/-15.1 mmHg, P<0.01). CONCLUSIONS: Administration of PTXF at the beginning of CPR improved macrocirculation, acid-base status and arterial oxygenation.

Smaller tidal volumes with room-air are not sufficient to ensure adequate oxygenation during bag-valve-mask ventilation.

The European Resuscitation Council has recommended decreasing tidal volume during basic life support ventilation from 800 to 1200 ml, as recommended by the American Heart Association, to 500 ml in order to minimise stomach inflation. However, if oxygen is not available at the scene of an emergency, and small tidal volumes are given during basic life support ventilation with a paediatric self-inflatable bag and room-air (21% oxygen), insufficient oxygenation and/or inadequate ventilation may result. When apnoea occurred after induction of anaesthesia, 40 patients were randomly allocated to room-air ventilation with either an adult (maximum volume, 1500 ml) or paediatric (maximum volume, 700 ml) self-inflatable bag for 5 min before intubation. When using an adult (n=20) versus paediatric (n=20) self-inflatable bag, mean +/-SEM tidal volumes and tidal volumes per kilogram were significantly (P<0.0001) larger (719+/-22 vs. 455+/-23 ml and 10.5+/-0.4 vs. 6.2+/-0.4 ml kg(-1), respectively). Compared with an adult self-inflatable bag, bag-valve-mask ventilation with room-air using a paediatric self-inflatable bag resulted in significantly (P<0.01) lower paO(2) values (73+/-4 vs. 87+/-4 mmHg), but comparable carbon dioxide elimination (40+/-2 vs. 37+/-1 mmHg; NS). In conclusion, our results indicate that smaller tidal volumes of approximately 6 ml kg(-1) ( approximately 500 ml) given with a paediatric self-inflatable bag and room-air maintain adequate carbon dioxide elimination, but do not result in sufficient oxygenation during bag-valve-mask ventilation. Thus, if small (6 ml kg(-1)) tidal volumes are being used during bag-valve-mask ventilation, additional oxygen is necessary. Accordingly, when additional oxygen during bag-valve-mask ventilation is not available, only large tidal volumes of approximately 11 ml kg(-1) were able to maintain both sufficient oxygenation and carbon dioxide elimination.

Postoperative dissociation of blood levels of cortisol and adrenocorticotropin after coronary artery bypass grafting surgery.

The regulation of the hypothalamo-pituitary-adrenal (HPA) axis in the operative and perioperative period of major surgical procedures is necessary for successful adaption to surgical stress. We report evidence on an altered response of HPA axis regulation in patients who underwent coronary artery bypass grafting (CABG) surgery. Plasma levels of adrenocorticotropin (ACTH), beta-endorphin, and cortisol were determined with radio-immune assay in 50 males for elective CABG surgery. The patients received general anesthesia using a balanced technique with sufentanil, isoflurane, and midazolam. Pre- and intraoperatively, there was no significant increase in plasma cortisol, ACTH, and beta-endorphin levels. On the evening of surgery, all plasma hormone levels were increased. On the evening of the first and second postoperative day, plasma ACTH and beta-endorphin levels returned to the preoperative baseline values. During the same time interval, plasma cortisol levels were significantly elevated and remained high until the end of the study period (p < 0.001). Our results indicate an altered regulation of the HPA axis in the postoperative period of patients after CABG surgery, as they are compatible with similar results in patients after major abdominal surgery, burned patients, and critically ill patients. Therefore, it is assumed that the finding of a postoperative dissociation between ACTH and cortisol is a result of the severity of perioperative adaptive mechanisms rather than of the specific conditions related to cardiac surgery.

Blood levels of corticosteroid-binding globulin, total cortisol and unbound cortisol in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass.

Previous studies have demonstrated a persistent rise in serum cortisol concentrations after cardiac surgery. To further investigate this finding and to evaluate the effect of hemodilution that occurs with the onset of cardiopulmonary bypass (CPB), concentrations of cortisol-binding globulin (CBG), total and unbound cortisol, and packed cell volume (PCV) were studied in 28 patients undergoing coronary artery bypass graft surgery. All patients received a standardized general anesthetic using a balanced technique with sufentanil, isoflurane, and midazolam. Blood was collected preoperatively, intraoperatively during CPB, and postoperatively in the evenings on the day of surgery and on the first and second postoperative day. Cortisol and CBG concentrations were measured by radioimmunoassay and were used to calculate the fraction of unbound cortisol. Serum CBG and cortisol concentrations corrected for hemodilution were significantly higher than non-corrected values. Perioperatively, CBG measurements were significantly intercorrelated. Intraoperatively, total and unbound cortisol concentrations were not significantly increased compared to preoperative values. Postoperatively up to the end of the study period serum concentrations of total and unbound cortisol were significantly increased compared to baseline values. Our results suggest that hemodilution occurs in all patients during cardiac surgery and continues up to the second postoperative day. This may lead to an underestimation of serum cortisol and CBG concentrations in patients undergoing heart surgery with CPB. Intraoperatively, concentrations of total and unbound cortisol were not significantly elevated. The postoperative rise in serum total cortisol concentration was accompanied by an increase in unbound cortisol concentration. The postoperative increase of unbound cortisol concentrations in patients undergoing cardiac surgery with CPB was largely due to an increase in cortisol secretion.

Clinical biochemical tissue monitoring during ischaemia and reperfusion in major vascular surgery.

BACKGROUND: Major vascular surgery with aortic cross-clamping is associated with temporary ischaemia of the lower limb due to lack of tissue blood flow. The present study was designed to determine if the short-term changes in cellular metabolism occurring during this situation can be detected by subcutaneous microdialysis. It was also hoped to ascertain if this new technique is useful in the continuous bedside monitoring of metabolism during aortic surgery. METHODS: In a controlled clinical study 20 patients undergoing elective aortic surgery were monitored using microdialysis probes that were inserted in the subcutaneous tissue of the left lower limb and a non-ischaemic region (shoulder). Interstitial fluid was obtained and the concentrations of glucose and lactate during lower limb ischaemia and during reperfusion were measured and compared with concentrations observed in fluid obtained from the non-ischaemic control tissue. RESULTS: Circulatory occlusion caused an immediate and significant decrease in the glucose/lactate ratio from 3.1+/-1.3 to 0.48+/-0.5 (P<0.05) that returned to preocclusion values within 2 h of commencing reperfusion. CONCLUSION: We suggest that microdialysis may be used both to assess acute changes in tissue metabolism during ischaemic periods and also to act as an additional tool for the detection of peri-operative acute variations in limb blood flow.

Effects of posture and positive airway pressure on plasma atrial natriuretic peptide and renal urodilatin excretion.

AIMS: To determine whether a coupling of plasma atrial natriuretic peptide (ANP) and renal excretion of urodilatin (U(URO)V)--recently observed during supraphysiological concentrations of ANP--may also be detected during moderate changes in ANP levels, i.e. if ANP is increased by supine positioning and decreased by applying continuous positive airway pressure (CPAP). MATERIAL AND METHODS: We investigated 10 healthy male volunteers, orally hydrated with 200 ml water/h, in a randomized crossover study for periods of 1 hour following 2 protocols. Protocol 1: sitting and supine position. Protocol 2: sitting with and without a CPAP of 8 cm H2O. RESULTS: ANP increased ongoing from the sitting to the supine position (SIT-1: 13.2 +/- 4.7; SUP: 27.9 +/- 21.9 pg x ml(-1); p < 0.01) during protocol 1 and decreased after the onset of CPAP in seated subjects (SIT-2: 16.9 +/- 7.9; SIT-CPAP: 13.9 +/- 6.5 pg x ml(-1); p < 0.05) during protocol 2. U(URO)V decreased slightly, but not significantly, during protocol I (SIT-1: 63.9 +/- 21.7; SUP: 49.9 +/- 13.2 fmol x min(-1)) and remained unchanged after institution of CPAP in the sitting position (SIT-2: 68.5 +/- 25.2; SIT-CPAP: 68.5 +/- 50.2 fmol x min(-1)). Correlation analysis revealed no relationship between plasma ANP and U(URO)V. CONCLUSIONS: Moderate variations in the levels of ANP in water-loaded volunteers do not induce parallel changes in the urinary excretion of urodilatin.