Summary

In anaesthetic practice we deal with cancer patients who are scheduled for operations on tumours or other manifestations of malignant disease. Those patients are often debilitated and have significant weight loss accompanied with hypoproteinaemia, anaemia and coagulation disorders. Oncological patients usually present to the anaesthetist before tumour disease surgery, but they are also candidates for elective operations (e.g. hernia repair) and urgent/emergency surgery (e.g. trauma, fractures and ileus). Chemotherapeutic agents given to these patients are potentially noxious, can affect the conduct of anaesthesia and, furthermore, may aggravate the patient's condition.

In this review the most commonly used cytostatic drug regimens and their common side-effects are listed. Some preclinical studies on anaesthetic and cytostatic drug metabolism and interactions are emphasized, as well as clinically relevant perioperative alterations that may affect anaesthetic management in cancer patients.

An anaesthetist may have to modify a routine anaesthetic regimen in cancer patients especially if anticancer chemotherapeutics were given. Clinically silent toxic drug effects may become apparent during operation, trauma or in the early postoperative course in such patients. Altered reactions to commonly used anaesthetics in patients receiving chemotherapeutics and an impaired stress reaction may occur in such patients. Special attention must be drawn to protection against opportunistic infections.

Summary

The treatment of critically ill patients has advanced markedly over the last decade. However, non-surgical bleeding of a diffuse nature from numerous tiny capillaries still remains a challenge. Once initiated, this type of bleeding may be troublesome and a vicious circle develops since it is not a single vessel contributing to this blood loss. The description ‘non-surgical blood loss’ is often given to this. This review describes a step-by-step approach for the treatment of non-surgical bleeding and includes various measures, such as desmopressin, blood components, antifibrinolytics, antithrombin III, prothrombin complex concentrates and factor XIII. While most non-surgical bleedings can be managed using the approach described here, a number of patients still continue to bleed. In these cases, the surgeon should re-evaluate the bleeding in terms of its surgical origin. If this can positively be excluded and if all of measures described fail to reduce or stop the bleeding, further treatment of such uncontrolled bleeding remains symptomatic.

Summary

Background and objective: To investigate the effects of barbiturates on batrachotoxin-modified sodium channels from different regions of the human heart. Single sodium channels from human atria were studied and compared with existing data from the human ventricle and from the central nervous system.

Methods: Sodium channels from preparations of human atrial muscle were incorporated into planar lipid bilayers in the presence of batrachotoxin, a sodium channel activator. The steady-state behaviour of single sodium channels was recorded in symmetrical 500 mmol NaCl before and after the addition of pentobarbital 0.34–1.34 mmol.

Results: The batrachotoxin-treated human atrial sodium channel had an average single-channel conductance of 23.8 ± 1.6 pS in symmetrical 500 mmol NaCl and a channel fractional open time of 0.83 ± 0.06. The activation mid-point potential was −98.0 ± 2.3 mV. Extracellular tetrodotoxin (a specific sodium channel blocking agent) blocked these channels with a k1/2 = 0.53 μmol at 0 mV. Pentobarbital reduced the time average conductance of single atrial sodium channels in a concentration-dependent manner (ID50 = 0.71 mmol). In the same way, the steady-state activation was shifted to more hyperpolarized potentials (−10.6 mV at 0.67 mmol pentobarbital).

Conclusions: The properties of batrachotoxin-modified sodium channels from human atrial tissue did not differ greatly from those described for ventricular sodium channels in the literature. Our data yielded no explanation for the observed functional diversity. However, cardiac sodium channels differ from those found in the central nervous system.

Summary

Background and objective: The growth of ambulatory surgical procedures is limited by severe postoperative pain. After particularly painful operative procedures, moderate-to-severe pain is estimated to occur in approximately 30% of patients. Inadequate analgesia may delay or prevent discharge, or result in readmission. Severe postoperative pain also causes extreme discomfort and can prevent sleep, thus contributing to postoperative fatigue. Moreover, postoperative pain limits mobility at home and delays the return to normal activities. The development of effective analgesia for postoperative pain is therefore a priority of modern medicine.

Results: The pain experienced during the first days spent at home is related to the magnitude of pain experienced at the hospital. Aggressive analgesic treatment at the hospital is therefore of key importance. This includes pre- and intraoperative administration of analgesics to reduce the pain in the immediate postoperative period, and the use of multimodal, balanced analgesia throughout recovery. Clinical studies have shown that patients who receive both pre- and postoperative analgesia experience greater pain relief than those who receive postoperative analgesia alone. Multimodal analgesia, including the use of anaesthetics, is increasingly important in attempts to avoid the prescription of single strong opioids postoperatively. The use of a non-steroidal anti-inflammatory drug (NSAID) plus an anaesthetic perioperatively has also been shown to be more effective than anaesthetic alone.

Conclusions: Postoperative pain is the most commonly reported complication of ambulatory surgery. Although the number of analgesic techniques seems more limited in outpatient than in inpatient surgery, the combination of analgesic regimens in a multimodal approach may improve postoperative analgesia and functional outcome after ambulatory surgery. The combination of acetaminophen plus tramadol is a useful formulation to prescribe if acetaminophen or NSAIDs alone are ineffective.

Summary

Sepsis is associated with a profound intravascular fluid deficit due to vasodilatation, venous pooling and capillary leakage. Fluid therapy is aimed at restoration of intravascular volume status, haemodynamic stability and organ perfusion. Circulatory stability following fluid resuscitation is usually achieved in the septic patient at the expense of tissue oedema formation that may significantly influence vital organ function. The type of fluid therapy, crystalloid or colloid, in sepsis with capillary leakage remains an area of intensive and controversial discussion. The current understanding of the physiology of increased microvascular permeability in health and sepsis is incomplete. Furthermore, there is a lack of appropriate clinical study end-points for fluid resuscitation. This review considers critically the clinical and experimental data analysing the assessment of capillary leakage in sepsis and investigating the effects of different fluid types on increased microvascular permeability in sepsis.

Summary

Background and objective: General anaesthesia may contribute to postoperative cognitive decline in the elderly. The aim was to determine the effects of repeated pentobarbital anaesthesia throughout life on central cholinergic function in the rat.

Methods: Young Lewis rats were randomly allocated to two groups. The anaesthesia group (n = 15) was anaesthetized with pentobarbital 20 mg kg−1 intraperitoneally at 6, 8.5, 11, 13.5, 16, 18.5, 21 and 23.5 months of age. The control group (n = 12) was treated identically, apart from the anaesthesia. At 26 months of age, the animals were killed and the brain dissected and stored for analysis. Central cholinergic function in the cortex and hippocampus was assessed by measuring [3H]-epibatidine and [125I]α-bungarotoxin binding to nicotinic receptors and choline acetyltransferase (ChAT) activity.

Results: Tissue from nine rats in the anaesthesia group and eight in the control group was available for analysis. There was a significant reduction in α-bungarotoxin binding in the anaesthetized compared with the control group in the superior cortex (P < 0.0002) and molecular cortex (P < 0.04). There were no significant differences between the groups for epibatidine binding or ChAT.

Conclusions: Repeated anaesthesia in rat reduces central nicotinic cholinergic binding in the cortex. The findings may have implications for postoperative cognitive function studies.

Summary

The use of muscle relaxants, considered until recently as common practice in current neurosurgical anaesthesia protocols, becomes increasingly more questionable today. The reasons rely on the evolution of neurosurgery including the advent of new surgical techniques, the evolution of anaesthesia having the benefit of new drugs and devices, and the rationale for using muscle relaxants balanced against their potential side-effects and possible pharmacodynamic alterations in neurosurgical patients.

Summary

Background and objective: Automatic tube compensation has been designed as a new ventilatory mode to compensate for the non-linear resistance of the endotracheal tube. The study investigated the effects of automatic tube compensation compared with breathing through a T-piece or pressure support during a trial of spontaneous breathing used for weaning patients from mechanical ventilation of the lungs.

Methods: Twelve patients were studied who were ready for weaning after prolonged mechanical ventilation (10.2 ± 8.4 days) due to acute respiratory failure. Patients with chronic obstructive pulmonary disease were excluded. Thirty minutes of automatic tube compensation were compared with 30 min periods of 7 cmH2O pressure support and T-piece breathing. Breathing patterns and workload indices were measured at the end of each study period.

Results: During T-piece breathing, the peak inspiratory flow rate (0.65 ± 0.20 L s−1) and minute ventilation (8.9 ± 2.7 L min−1) were lower than during either pressure support (peak inspiratory flow rate 0.81 ± 0.25 L s−1; minute ventilation 10.2 ± 2.3 L min−1, respectively) or automatic tube compensation (peak inspiratory flow rate 0.75 ± 0.26 L s−1; minute ventilation 10.8 ± 2.7 L min−1). The pressure–time product as well as patients' work of breathing were comparable during automatic tube compensation (pressure–time product 214.5 ± 104.6 cmH2O s−1 min−1, patient work of breathing 1.1 ± 0.4 J L−1) and T-piece breathing (pressure–time product 208.3 ± 121.6 cmH2O s−1 min−1, patient work of breathing 1.1 ± 0.4 J L−1), whereas pressure support resulted in a significant decrease in workload indices (pressure–time product 121.2 ± 64.1 cmH2O s−1 min−1, patient work of breathing 0.7 ± 0.4 J L−1).

Conclusions: In weaning from mechanical lung ventilation, patients' work of breathing during spontaneous breathing trials is clearly reduced by the application of pressure support 7 cmH2O, whereas the workload during automatic tube compensation corresponded closely to the values during trials of breathing through a T-piece.

Summary

Background and objective: An inverse I : E ratio (inspiratory time > expiratory time) may have benefits in patients suffering trauma who requiring lung ventilation. However, this application may be deleterious if there is concomitant head injury. We aimed to determine the physiological effects of pressure- and volume-controlled modes of inverse ratio (I : E = 2 : 1) ventilation of the lungs, while maintaining normocapnia, in a rabbit model of raised intracranial pressure (ICP).

Methods: New Zealand White rabbits were anaesthetized with isoflurane and a tracheostomy was performed. Subarachnoid haemorrhage was simulated in two groups by injecting blood into the cisterna magna. Groups 1 and 2 (n = 6, each), controls, were compared with Groups 3 and 4 (n = 6, each) with the simulated subarachnoid haemorrhage. Each ventilation mode was used with an I : E ratio of 2 : 1 for 30 min. Mean arterial pressure (MAP), ICP, cerebral perfusion pressure (CPP), mean airway pressure (PAW) and arterial blood-gas status were measured.

Results: Both modes increased mean PAW (P < 0.02). This increase was greater with the volume-controlled mode (P < 0.02). The baseline value averaged 5.8 ± 0.4 and 5.6 ± 0.3 mmHg in Groups 3 and 4, respectively, and increased to 7.8 ± 0.3 and 10.8 ± 0.4 mmHg. Inducing subarachnoid haemorrhage increased ICP and MAP (P < 0.02). Baseline ICPs were 10.3 ± 0.5 and 10.3 ± 0.4 mmHg in Groups 1 and 2, respectively, whereas they were 25.4 ± 1.2 and 25.8 ± 0.8 mmHg in Groups 3 and 4. However, ICP, MAP and CPP did not differ significantly according to the mode.

Conclusions: An already raised ICP was altered by the application of induced mean PAW increases as a consequence of inverse ratio ventilation of the lungs with normocapnia.

Summary

Background and objective: Oral fixed drug combination analgesics have potential advantages over monotherapy, but these can only be attained through careful design.

Results: The main reasons for developing combination analgesics are to gain efficacy and to reduce toxicity. Analgesic combinations interact pharmacokinetically, or pharmacodynamically, or both, in positive or negative terms. The tmax value for both enantiomers of tramadol occur two hours following administration, and that for the active, (+)-M1 metabolite occurs after three hours. Thus, pairing tramadol with acetaminophen, a rapid-onset analgesic, represents a pharmacokinetically rational combination. Analgesic combinations should satisfy two important pharmacodynamic criteria: the components of the combination should display additive or synergistic analgesia; and this interaction should allow lower doses of each substance to be used in combination, resulting in an improved safety profile. Clinical studies of the pharmacodynamic between oral tramadol and acetaminophen in third molar extraction and cold pressor models have provided evidence that this combination provides better efficacy than either individual component of the combination.

Conclusions: In summary, combination analgesics can play a valuable role in pain management. However, dubious combinations (directed against the same targets or with unwanted interactions) and ‘old fashioned’ fixed-dose multiple analgesic agent combinations should be avoided. Fixed-dose combination analgesics are of value only when they have been developed according to rational pharmacokinetic and pharmacodynamic criteria, and when claims for their benefits have been supported by evidence-based data and well-designed clinical studies.

Summary

Background and objective: The efficacy of the Trendelenburg position, a common first step to treat suspected hypovolaemia, remains controversial. We evaluated its haemodynamic effects on cardiac preload and performance in patients after cardiac surgery.

Methods: Twelve patients undergoing mechanical ventilation of the lungs who demonstrated left ventricular ‘kissing papillary muscles’ by transoesophageal echocardiography, thus suggesting hypovolaemia, were positioned 30° head down for 15 min immediately after cardiac surgery. Cardiac output by thermodilution, central venous pressure, pulmonary artery occlusion pressure, left ventricular end-diastolic area by transoesophageal echocardiography and intrathoracic blood volume by thermo- and dye dilution were determined before, during and after this Trendelenburg manoeuvre.

Results: Trendelenburg's manoeuvre was associated with increases in central venous pressure (9 ± 2 to 12 ± 3 mmHg) and pulmonary artery occlusion pressure (8 ± 2 to 11 ± 3 mmHg). The intrathoracic blood volume index increased slightly (dye dilution from 836 ± 129 to 872 ± 112 mL m−2; thermodilution from 823 ± 129 to 850 ± 131 mL m−2) as did the left ventricular end-diastolic area index (7.5 ± 2.1 to 8.1 ± 1.7 cm2 m−2), whereas mean arterial pressure and the cardiac index did not change significantly. After supine repositioning, the cardiac index decreased significantly below baseline (3.0 ± 0.6 versus 3.5 ± 0.8 L min−1 m−2) as did mean arterial pressure (76 ± 12 versus 85 ± 11 mmHg), central venous pressure (8 ± 2 mmHg) and pulmonary artery occlusion pressure (6 ± 4 mmHg). The intrathoracic blood volume index and left ventricular end-diastolic area index did not differ significantly from baseline.

Conclusions: Trendelenburg's manoeuvre caused only a slight increase of preload volume, despite marked increases in cardiac-filling pressures, without significantly improving cardiac performance.

Summary

Background and objective: The advantages of albumin over less costly alternative fluids continue to be debated. Meta-analyses focusing on survival have been inconclusive, and other clinically relevant end-points have not been systematically addressed. We sought to determine whether albumin confers significant clinical benefit in acute illness compared with other fluid regimens.

Methods: Database searches (MEDLINE, EMBASE, Cochrane Library) and other methods were used to identify randomized controlled trials comparing albumin with crystalloid, artificial colloid, no albumin or lower-dose albumin. Major findings for all end-points were extracted and summarized. A quantitative meta-analysis was not attempted.

Results: Seventy-nine randomized trials with a total of 4755 patients were included. No significant treatment effects were detectable in 20/79 (25%) trials. In cardiac surgery, albumin administration resulted in lower fluid requirements, higher colloid oncotic pressure, reduced pulmonary oedema with respiratory impairment and greater haemodilution compared with crystalloid and hydroxyethylstarch increased postoperative bleeding. In non-cardiac surgery, fluid requirements, and pulmonary and intestinal oedema were decreased by albumin compared with crystalloid. In hypoalbuminaemia, higher doses of albumin reduced morbidity. In ascites, albumin reduced haemodynamic derangements, morbidity and length of stay and improved survival after spontaneous bacterial peritonitis. In sepsis, albumin decreased pulmonary oedema and respiratory dysfunction compared with crystalloid, while hydroxyethylstarch induced abnormalities of haemostasis. Complications were lowered by albumin compared with crystalloid in burn patients. Albumin-containing therapeutic regimens improved outcomes after brain injury.

Conclusions: Albumin can bestow benefit in diverse clinical settings. Further trials are warranted to delineate optimal fluid regimens, in particular indications.

Summary

Background and objective: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78–94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine. This multicentre study was designed to investigate whether an in vitro contracture test with bolus administration of 4-chloro-m-cresol can improve the accuracy of the diagnosis of susceptibility to MH.

Methods: Three hundred and fifty-two patients from 11 European MH laboratories participated in the study. The patients were first classified as MH susceptible, MH normal or MH equivocal by the in vitro contracture test according to the European MH protocol. Muscle specimens surplus to diagnostic requirements were used in this study (MH susceptible = 103 viable samples; MH equivocal = 51; MH normal = 204). 4-Chloro-m-cresol was added to achieve a concentration of 75 μmol L−1 in the tissue bath. The in vitro effects on contracture development and muscle twitch were observed for 60 min.

Results: After bolus administration of 4-chloro-m-cresol, 75 μmol L−1, 99 of 103 MH-susceptible specimens developed marked muscle contractures. In contrast, only two of 204 MH-normal specimens showed an insignificant contracture development following 4-chloro-m-cresol. From these results, a sensitivity rate of 96.1% and a specificity rate of 99.0% can be calculated for the in vitro contracture test with bolus administration of 4-chloro-m-cresol 75 μmol L−1. Forty-three patients were diagnosed as MH equivocal, but only specimens from 16 patients developed contractures in response to 4-chloro-m-cresol, indicating susceptibility to MH.

Conclusions: The in vitro contracture test with halothane and caffeine is well standardized in the European and North American test protocols. However, this conventional test method is associated with the risk of false test results. Therefore, an improvement in the diagnosis of MH is needed. Regarding the results from this multicentre study, the use of 4-chloro-m-cresol could increase the reliability of in vitro contracture testing.

Summary

Background and objective: Desflurane has been shown to increase sympathetic activity and heart rate (HR) in a concentration-dependent manner. Nevertheless, desflurane, like all other volatile anaesthetics, increased HR in parallel to vagal inhibition in a previous study. Therefore, our hypothesis is that desflurane elicits tachycardia by vagal inhibition rather than by activation of the sympathetic nervous system.

Methods: Six dogs were studied awake and during desflurane anaesthesia (1 and 2 MAC) alone, after pre-treatment with propranolol (2 mg kg−1 followed by 1 mg kg−1 h−1), or after pre-treatment with atropine (0.1 mg kg−1 followed by 0.05 mg kg−1 h−1). The effects on HR and HR variability were compared by an analysis of variance (P < 0.05). HR variability was analysed in the frequency domain as power in the high-(0.15–0.5 Hz, vagal activity) and low-frequency range (0.04–0.15 Hz, sympathetic and vagal activity).

Results: HR increased during 2 MAC of desflurane from about 60 (awake) to 118 ± 2 beats min−1 (mean ± SEM) in controls and to 106 ± 3 beats min−1 in dogs pre-treated with propranolol. In contrast, pre-treatment with atropine increased HR from 64 ± 2 to 147 ± 5 beats min−1 (awake) and HR decreased to 120 ± 5 beats min−1 after adding desflurane. High-frequency power correlated inversely with HR (r2 = 0.95/0.93) during desflurane alone and in the presence of β-adrenoceptor blockade, with no significant difference between regression lines. There was no correlation between these variables during atropine/desflurane.

Conclusions: The increase in HR elicited by desflurane mainly results from vagal inhibition and not from sympathetic activation.

Summary

Background and objective: The effects of xenon on mesenteric vascular resistance have not been investigated. Because human beings anaesthetized with xenon show good cardiovascular stability, we believed that the agent would have little or no effect on vascular resistance in the splanchnic bed. We determined the effects of different inhaled xenon concentrations on mesenteric blood flow and mesenteric oxygen consumption in pigs sedated with intravenous propofol.

Methods: Twenty-three minipigs were instrumented with transit time flow probes around the pulmonary and superior mesenteric arteries as well as with pulmonary artery and portal venous catheters. A 14 h recovery was allowed followed by recordings of baseline values. Xenon was then randomly administered in 0.30, 0.50, and 0.70 end-tidal fractions.

Results: The administration of xenon resulted in an 8% (not dose dependent) decrease in mean arterial pressure (from 99 ± 15 to 91 ± 19 mmHg; P < 0.05), a 20% decrease in calculated systemic oxygen consumption (from 0.23 ± 0.07 to 0.19 ± 0.04 L min−1; P < 0.01), a 20% reduction in mesenteric oxygen delivery (from 41 ± 12 to 33 ± 11 mL min−1; P < 0.001), a 37% reduction in mesenteric metabolic rate of oxygen (from 11.3 ± 3.6 to 7.1 ± 3.2 mL min−1; P < 0.01) and an 8% decrease in mesenteric artery blood flow (0.22 ± 0.07 to 0.20 ± 0.07 L min−1; P < 0.05) in a dose-dependent fashion. Heart rate, cardiac output, systemic vascular resistance, mesenteric vascular resistance, mesenteric oxygen extraction fraction and portal lactate concentration were not significantly altered by xenon.

Conclusions: Xenon inhalation in the propofol-sedated pig had no measurable effects on mesenteric vascular resistance. This finding may partly explain the well-known cardiovascular stability observed in patients anaesthetized with xenon. Although mesenteric artery blood flow and mesenteric oxygen delivery decreased during xenon administration, unchanged mesenteric oxygen extraction fraction and portal lactate suggest that metabolic regulation of the splanchnic circulation remained unaltered.

Summary

Background and objective: Administration of calcium safely and effectively reverses many of the electrophysiological actions of hyperkalaemia, but it has not been studied for pretreatment. Based on cellular studies, magnesium also has been suggested to prevent the effects of potassium on the heart. As their mechanisms of action differ, a combination of these drugs might have a synergistic protective action. Both compounds are inexpensive and can be administered safely in modest doses. We investigated whether magnesium, calcium or their combination could protect against hyperkalaemic cardiac arrest.

Methods: Twenty-four adult rats were anaesthetized with halothane and randomly pretreated with CaCl2 15 mg kg−1, MgSO4 30 mg kg−1, CaCl2 7.5 mg kg−1 + MgSO4 15 mg kg−1 or physiological saline. Potassium (0.01 mmol kg−1 h−1) was infused. The times to the first dysrhythmia, mean arterial pressure decrease to <40% of baseline and cardiovascular collapse were measured.

Results: Serum potassium concentrations increased to similar values in all groups (to 12.0 ± 0.2 mmol L−1 at the time of collapse). No differences in survival times were observed between groups. There was a trend for respiratory values to be better in the group receiving magnesium.

Conclusions: Pretreatment with magnesium, calcium or a combination of both did not influence the time to cardiovascular collapse, and is therefore – at least in our model – not of any benefit in preventing hyperkalaemic cardiac arrest.

Summary

Background and objective: The effect of propofol on myocardial dysfunction during ischaemia and reperfusion is controversial yet important because of its frequent use in cardiac anaesthesia. Although animal studies suggest a free radical-scavenging potential, the cardioprotective properties of propofol have not been demonstrated consistently in vivo. Previous studies focused on systolic function while diastolic function may be a more sensitive marker of ischaemic injury. The main aim was to document the effect of propofol on diastolic function in isolated, blood perfused rabbit hearts subjected to moderate global ischaemia and reperfusion.

Methods: Propofol 168 μmol L−1, or the equivalent of its vehicle, Intralipid®, was administered to 34 paced parabiotic Langendorff blood-perfused isolated rabbit hearts before and after 30 min of global normothermic ischaemia. Recovery of systolic function was quantified with the maximum rate of rise of left ventricular pressure. Diastolic performance was assessed using the time constant of the decline in left ventricular pressure (τ) and chamber stiffness (VdP/dV at 12 mmHg).

Results: Recovery of systolic function during reperfusion was comparable in the two groups. There was no difference in left ventricular pressure between the two groups at any time during the experiments. Chamber stiffness increased significantly during ischaemia and reperfusion in the control group (from 34 ± 9 to 54 ± 8 mmHg during ischaemia, and 43 ± 5 mmHg after 30 min reperfusion; mean ±95% confidence interval) but not in the propofol-treated group (29 ± 5, 36 ± 8 and 30 ± 8 at baseline, ischaemia and 30 min reperfusion, respectively).

Conclusions: Propofol has no protective effect on active relaxation or on systolic function in the present model, but it reduces ischaemic and postischaemic chamber stiffness.

Summary

Background and objective: A variable incidence rate of renal dysfunction (3–35%) after cardiac surgery with cardiopulmonary bypass has been reported. The aim was to define the typical pattern of renal dysfunction that follows coronary surgery with cardiopulmonary bypass using albumin, immunoglobulin (IgG), α1-microglobulin and β-glucosaminidase (β-NAG) excretion as indicators.

Methods: Twenty patients with preoperative normal renal function, defined by plasma creatinine, creatinine clearance, fractional excretion of sodium and renal excretion of proteins, undergoing elective myocardial revascularization surgery with cardiopulmonary bypass, were prospectively studied. Variables recorded were demographic and haemodynamic variables, duration of cardiopulmonary bypass and aortic clamping, intra- and postoperative urine output, plasma creatinine concentration, creatinine clearance and excretion of sodium, albumin, IgG, β-glucosaminidase (β-NAG), and β-microglobulin. Measurements were made preoperatively, immediately before and then during and immediately after cardiopulmonary bypass, and again at 1, 24, 72 h, 7 and 40 days following surgery.

Results: Albumin and IgG excretion rose significantly during cardiopulmonary bypass (P < 0.05), remaining at these levels at 24 h postoperatively. An increase of α1-microglobulin and β-NAG concentrations was observed during cardiopulmonary bypass (P < 0.05), which were maintained until the seventh postoperative day and remained elevated in some patients at the 40th postoperative day. This correlated with preoperative diabetes mellitus (P < 0.001), low cardiac output after cardiopulmonary bypass (P < 0.001) and the duration of stay in the intensive care unit (P < 0.001).

Conclusions: The pattern of renal dysfunction after cardiopulmonary bypass for myocardial revascularization is characterized by temporary renal dysfunction at both glomerular and tubular levels with an onset within 24 h of surgery and which lasts between 24 h and 40 days, respectively, following surgery.

Summary

Background and objective: Benzodiazepines may cause hypotension and are reported to interfere with smooth vascular muscle activity. The aim was to elucidate the influence of three different benzodiazepines on the vascular reactivity of coronary arteries.

Methods: Using the model of isolated vessels, we studied the impact of midazolam (0.15, 1.5, 15 μg mL−1), diazepam (0.1, 1.0, 10 μg mL−1) and flunitrazepam (0.01, 0.1, 1.0 μg mL−1) on the contractile responses to histamine (2 × 10−5 mol L−1) and serotonin (3 × 10−5mol L−1) in isolated intact and denuded coronary arteries.

Results: Midazolam significantly attenuated the contractile response when administered in high concentrations (15 μg mL−1). This effect was more pronounced in intact than in denuded preparations (histamine: −22.7 versus −7.3%, P = 0.0079; serotonin: −47.1 versus −15.9%, P < 0.0001). Diazepam and flunitrazepam exerted no significant effects on the vascular tone of coronary arteries.

Conclusions: Midazolam, but not diazepam or flunitrazepam, attenuates the contractile responses to vasoconstrictors in concentrations beyond those used in clinical practice. This effect is in part mediated by endothelial factors.

Summary

Background and objective: The Doppler-derived echocardiographic TEI-index, defined as the sum of the left ventricular isovolumic contraction and isovolumic relaxation times divided by ejection time, quantifies combined systolic and diastolic ventricular functions. The index has been proposed to be independent of arterial pressure and heart rate, implying a broad clinical usefulness. However, it is unclear whether the index is preload independent. We assessed whether and to what degree the TEI-index is altered by left ventricular loading conditions, and the feasibility of measurement by transoesophageal echocardiography during anaesthesia and mechanical ventilation.

Methods: We studied 17 anaesthetized mechanically ventilated patients with coronary artery disease during variations in left ventricular preload evoked by head-up and head-down tilt, respectively.

Results: A head-down tilt increasing left ventricular end-diastolic area from 18.8 ± 4 to 23.7 ± 4 cm2 (P < 0.05) significantly decreased the TEI-index from 0.5 ± 0.17 to 0.33 ± 0.15 (P < 0.05). In contrast, the TEI-index remained unchanged with decreased left ventricular preload (14.4 ± 3.7 cm2) during head-up tilt.

Conclusions: An increase in preload decreases the TEI-index indicating its sensitivity to acute increases in left ventricular preload. The TEI-index can be measured perioperatively by transoesophageal echocardiography.