Is postspinal hypotension a sign of impaired cardiac performance in the elderly? An observational mechanistic study.

Background: We have previously reported that stroke volume is reduced in a majority of elderly patients undergoing surgical repair of hip fracture before and after intrathecal injection of anaesthetic. We aimed to investigate these observations further in a prospective study of elderly patients undergoing elective hip or knee arthroplasty under spinal anaesthesia. Methods: Patients ≥65 yr undergoing elective arthroplasty were monitored with LiDCOplus™ preoperatively (baseline), before and continuously for 45 min after spinal anaesthesia. Postspinal hypotension was defined as systolic blood pressure (bp) < 100 mm Hg or > 30% decrease from baseline. Associations between post-spinal hypotension and haemodynamic changes before (i.e. between baseline and before injection) spinal anaesthesia were analysed by logistic regression analysis. Results: Twenty patients with a mean age of 74 (range 66-89) yr were included. Stroke volume index decreased by 14% (95% CI 9.3%-19%) before spinal anaesthesia. When patients were categorised according to post-spinal hypotension (Y/N) the patterns of haemodynamic changes differed. In the hypotensive patients, cardiac index progressively decreased whereas it increased initially in the non-hypotensive patients. Reduction of cardiac index from baseline before spinal anaesthesia was associated with increased risk of hypotension: OR 0.79 (95% CI 0.60, 0.91). The predictive value of reduced cardiac index was good (AUC under ROC curve 0.91). Conclusions: A decrease in cardiac output from baseline before spinal anaesthesia and an inability to increase it after induction may be important features of postspinal hypotension in elderly patients.

Towards individualized perioperative, goal-directed haemodynamic algorithms for patients of advanced age: observations during a randomized controlled trial (NCT01141894).

BACKGROUND: During a previous study on intraoperative goal-directed haemodynamic treatment (GDHT) in elderly patients, cardiac performance did not improve as anticipated (ClinicalTrials.gov NCT01141894). We hypothesized that in this group, responsiveness to interventions could be predicted by individual patient characteristics. METHODS: Data for the present study were collected during a previously performed, single-centre, open, randomized, and controlled parallel-group superiority trial in patients aged ≥70 yr undergoing hip-fracture surgery. Haemodynamic parameters were collected by the LiDCOplus™ monitor. The GDHT group received oxygen delivery-guided fluid challenges and dobutamine infusion. Management in the routine fluid treatment group was clinician guided without access to LiDCOplus™ readings. In the GDHT group, independent predictors were assessed by multiple logistic regression analyses of two outcomes: first fluid challenge response (defined as increase of stroke volume by ≥10%); and overall intervention response (maintenance of oxygen delivery at the end of surgery). RESULTS: Data from 72 routine fluid treatment and 70 GDHT patients were analysed. Clinician-guided pre-anaesthesia fluid loading increased the stroke volume in 14% of patients, and 17% of patients increased or maintained oxygen delivery at the end of surgery. The GDHT-guided first and subsequent fluid challenges were associated with increased stroke volume in 39 and 9% of patients, respectively, and increased or maintained oxygen delivery was present in 47% of patients at the end of surgery. In the GDHT group, a baseline stroke volume index (<28 ml m(-2)) was an independent predictor of first fluid challenge response, and a baseline oxygen delivery index (<330 ml min(-1) m(-2)) was a predictor of maintained or increased oxygen delivery. CONCLUSIONS: Fewer patients responded to GDHT than anticipated. Our data suggest that individual characteristics could predict the haemodynamic responses. CLINICAL TRIAL REGISTRATION: NCT01141894.

[Interobserver variability study for daily cone beam computed tomography registration of prostate volumetric modulated arc therapy]. / Tomographie conique quotidienne pour les traitements pelviens et prostatiques: étude interobservateurs.

PURPOSE: This work evaluated the interobserver variability in cone beam computed tomography (CBCT) registration for prostate cancers treated with intensity-modulated radiotherapy. MATERIAL AND METHODS: Twelve technologists realized 286 CBCT/CT registrations (bone registration followed by prostate to prostate registration). The registration results were compared to those obtained by two radiation oncologists (reference). Each technologist reported the shifts calculated by the software in all three axes. A statistical analysis allowed us to calculate the minimum threshold under which 95% of the observers found similar values. A variance analysis followed by the post hoc test were used to find differences in interobserver registration variability and determine whether any individual users performed registrations which differed significantly from those of the other users. RESULTS: The registration differences compared to the reference in the three directions in terms of 95th percentile are: 2.1mm left-right, 3.5mm target-gun, 7.3mm anterior-posterior. In the posterior direction, 4% of the observers have found differences superior to 8mm, margin used in routine without the use of a daily CBCT. The variance test revealed a P-value <0.05 only for target-gun and for all observers there was no significant difference compared to the reference. CONCLUSION: This study confirmed the interest of a 3D tissue registration for prostate treatments. The registration study showed a good interobserver reproducibility. This showed the importance of a daily CBCT/CT registration in prostate treatment with the possibility of a planning target volume margin reduction in the three directions. An evaluation of a partial delegation of registration to technologists should be done by the radiation oncologists.

Randomized controlled trial of goal-directed haemodynamic treatment in patients with proximal femoral fracture.

BACKGROUND: Patients with proximal femoral fracture (PFF) are at high risk of postoperative complications. Goal-directed haemodynamic treatment (GDHT) in other high-risk surgical patients reduces postoperative complications. We aimed to compare effects of GDHT and routine fluid treatment (RFT) on postoperative outcomes after PFF surgery. METHODS: PFF patients (≥70 yr) were enrolled in this single-centre, open, randomized, controlled, parallel-group superiority trial with concealed allocation using computer-generated randomization. TREATMENTS: (i) GDHT to attain oxygen delivery index >600 ml min(-1) m(-2) using fluids and dobutamine and (ii) a protocol-guided RFT. After 150 enrolled patients, the trial was stopped due to slow recruitment. The short-term primary outcome measure was the relative risk (RR) of postoperative complications; secondary measures were (i) administered fluid levels, (ii) vasopressor requirements, and (iii) haemodynamic responses. RESULTS: For the GDHT group, 74 and for the RFT group 75 patients were designated. The RR of postoperative complications (GDHT vs RFT) was 0.79 (95% confidence interval 0.54-1.16); the volumes of i.v. fluids decreased (1078 vs 1440 ml, P=0.01); fewer patients required treatment of hypotension (18.5% vs 75%, P<0.005); there were more patients with increased oxygen delivery at the end of operation (28% vs 8%, P=0.04), but the haemodynamic goal was achieved in only 27% of patients in the GDHT group. CONCLUSIONS: The magnitude of risk reduction of postoperative complications is clinically relevant, but the trial was underpowered and the null hypothesis cannot be rejected.

Could benefits of epidural analgesia following oesophagectomy be measured by perceived perioperative patient workload?

BACKGROUND: A controversy exists whether beneficial analgesic effects of epidural analgesia over intravenous analgesia influence the rate of post-operative complications and the length of hospital stay. There is some evidence that favours epidural analgesia following major surgery in high-risk patients. However, there is a controversy as to whether epidural analgesia reduces the intensive care resources following major surgery. In this study, we aimed at comparing the post-operative costs of intensive care in patients receiving epidural or intravenous analgesia. METHODS: Clinical data and rates of post-operative complications were extracted from a previously reported trial following thoraco-abdominal oesophagectomy. Cost data for individual patients included in that trial were retrospectively obtained from administrative records. Two separate phases were defined: costs of pain treatment and the direct cost of intensive care. RESULTS: Higher calculated costs of epidural vs. intravenous pain treatment, 1,037 vs. 410 Euros / patient, were outweighed by lower post-operative costs of intensive care 5,571 vs. 7,921 Euros / patient (NS). CONCLUSION: Higher costs and better analgesic effects of epidural analgesia compared with intravenous analgesia do not reduce total costs for post-operative care following major surgery.

Evaluation of costs and effects of epidural analgesia and patient-controlled intravenous analgesia after major abdominal surgery.

BACKGROUND: The outcome of different treatment strategies for postoperative pain has been an issue of controversy. Apart from efficacy and effectiveness a policy decision should also consider cost-effectiveness. Since economic analyses on postoperative pain treatment are rare we developed a decision model in a pilot cost-effectiveness analysis (CEA) comparing epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) after major abdominal surgery in routine care. METHODS: Using a decision-tree model, treatment with EDA (ropivacaine and morphine) was compared with PCIA (morphine). Effects and costs of treatment were established. The number of pain-free days at rest (pain intensity <30 using visual analogue scale 1-100 mm) was the primary measure of effect. An incremental cost-effectiveness ratio (ICER) was calculated as the difference in direct costs divided by the difference in effect. A database on 644 patients collected for the purpose of quality control during the period of 1997 to 1999 was the main data source. Sensitivity analysis was used to test uncertain data. RESULTS: EDA was more effective in terms of pain-free days but more expensive. The additional cost for each pain-free day was 5652 Euros. CONCLUSION: It is a judgement of value if the additional cost is reasonable. When the cost of around 55,000 Euros per gained life-year with full health for other interventions is debated, our result indicates poor cost-effectiveness for EDA. Before any conclusion can be drawn concerning policy recommendations the difference in costs has to be related to other outcome measures as length of hospital stay, morbidity and mortality are required.

[Experience with surgical treatment of prosthetic valve endocarditis]. / Múbillentyú-endocarditis sebészi kezelésével szerzett tapasztalataink.

Prosthetic valve endocarditis (PVE) is a rare but dangerous complication that may occur after the implantation. The authors retrospectively summarize their 11-year experience in treating PVE. 2357 prosthetic valve (PV) implantations were performed over 11 years at the Department of Cardiovascular Surgery, Semmelweis University, Budapest, PVE was found to be the indication for operation in 1.8% of the cases (43/2357). 43 surgical interventions were carried out on 38 patients (mean age: 52.5 yrs, male/female ratio: 25/13). Blood cultures were positive in 86% and negative in 14% of the cases. The infected PV-s were replaced emergently (14%), urgently (79%) or electively (7%). The explanted valves were aortic in 55% and mitral 45% of the cases, 63% were mechanical and 37% biological. PVE followed the primary PV implantation in less than a year in 39.5%. Infected environment during the primary PV implantation was found to be a predisposing factor for the late endocarditis episodes. The mean age of the infected and explanted aortic bioprosthetic valves was significantly higher than that of explanted mechanical valves (p < 0.05). No such difference could be found at the mitral valves. The explanted valves were replaced by mechanical (75.5%) or biological (22.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%. Endocarditis reoccurred in 20% of the cases. Means follow-up duration was 45.5 months. Two-, five- an 10-year survival were 75%, 64% and 51% respectively. In conclusion in the surgical treatment of PVE, bioprosthetic and mechanical valves are suitable alternatives as opposed to homografts and freestyle stentless valves.

[Biventicular pacing in patients with severe heart failure]. / Súlyos szívelégtelenség kezelése biventricularis ingerléssel.

According to initial clinical results biventricular pacing seems to be effective in the treatment of patients suffering from drug refractory severe heart failure combined with intraventricular conduction disturbance. Biventricular cardioverter defibrillators and biventricular pacemakers were implanted in patients suffering from drug refractory severe heart failure in 3 and in 2 cases, respectively (follow up > 6 months). NYHA III-IV functional class, low left ventricular ejection fraction (23.2 +/- 5.4%), wide QRS (> 150 ms) with left bundle branch block and lateral dyssynchrony were present in each case. The left ventricle was enlarged in each patient (end-diastolic/end-systolic diameter: 78.6 +/- 9.2/66.2 +/- 8.1 mm). The indications of cardioverter defibrillator implantations were both sustained ventricular tachycardia and ventricular fibrillation, nonsustained ventricular tachycardia combined with syncope in 2 and in 1 case, respectively. The duration of QRS decreased (190 +/- 36 vs. 134 +/- 17 ms, p = 0.012) and wall movement disorder disappeared. At the last follow up every patients were in NYHA II functional class and a decrease in left ventricular diameter could be observed (end-diastolic: 72 +/- 10.4 mm, p = 0.07; end-systolic: 62 +/- 10 mm, p = 0.09). During the follow up period (7.3 +/- 1.7 months) 18 episodes of ventricular arrhythmias could be detected in the same patient. Biventricular pacemakers and cardioverter defibrillators were implanted and applied successfully in the treatment of congestive heart failure for the first time in Hungary. The effect of biventricular pacing on morbidity and mortality, the cost-effectiveness, the exact indication and the combined use with cardioverter defibrillator have yet to be proven in future randomized trials.

[Multichamber pacing--a new non-pharmacologic method for the treatment of severe heart failure]. / Többüregú ingerlés--a súlyos szívelégtelenség kezelésének új nonfarmakológiás módszere.

According to initial clinical results biventricular pacing seems to be effective in the treatment of patients suffering from drug refractory severe heart failure combined with intraventricular conduction disturbance. Biventricular cardioverter defibrillators and biventricular pacemakers were implanted in patients suffering from drug refractory severe heart failure in 10 and in 15 cases, respectively. NYHA III-IV functional class, low left ventricular ejection fraction (24.2 +/- 6%), wide QRS (> 150 ms) with left bundle branch block and lateral dyssynchrony were present in each case. The left ventricle was enlarged in each patient (endodiastolic/endsystolic diameter: 78.6 +/- 9.2/68.2 +/- 8.3). The indications of cardioverter defibrillator implantations were both sustained ventricular tachycardia and ventricular fibrillation, nonsustained ventricular tachycardia combined with syncope in 7 and in 3 case, respectively. The duration of QRS decreased (187 +/- 32 vs. 136 +/- 19 ms, p = 0.012) and wall movement disorder disappeared. At the last follow up every patients were in NYHA II functional class and a decrease in left ventricular diameter could be observed (endodiastolic: 70.3 +/- 9.1 mm, p = 0.04; endosystolic: 61.9 +/- 8.8 mm, p = 0.04). During the follow up period (8.8 +/- 5.1 months) 18 episodes of ventricular arrhythmias were detected in the same patient, 2 patients died (1 arrhythmia death, 1 sudden cardiac death). Biventricular pacemakers and cardioverter defibrillators were implanted and applied successfully in the treatment of congestive heart failure for the first time in Hungary.

Neuroprotective effect of GYKI 52466 on AMPA-induced neurotoxicity in rat striatum.

The neuroprotective effect of intraperitonally administered GYKI 52466 (2,3-benzodiazepine derivate) was investigated on AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxalon-propionic acid)-induced neuronal degeneration in the striatum of adult rats. The dose-dependent neurotoxic effect of AMPA was evaluated by the decrease in the activity of choline acetyltransferase (ChAT), due to degeneration of cholinergic neurons. An injection of 25 mg/kg GYKI 52466 30 min prior to the striatal application of 50 nmol AMPA, followed by repeated application of GYKI 52466 (10 times 5 mg/kg at 10 min intervals, reaching a final dose of 75 mg/kg) was able to prevent neuronal damage monitored by ChAT activity. Conversely, co-injection of GYKI 52466 (50 and 75 mg/kg) with AMPA (50 and 100 nmol) did not elicit any significant protection against the neuronal loss as measured by the ChAT enzyme activity. Therefore, one dose of agonist decreasing ChAT activity by about 40% (50 nmol) was tested on [3H]girisopam binding sites and on the immunoreactivity of glial fibrillary acid protein. The lesions were measured on methylene blue-stained serial sections with a computer assisted image analysis program (NIH Image 1.60). As a result of the AMPA treatment [3H]girisopam binding sites became depleted, and the immunoreactivity of glial fibrillary acid protein increased and on the site of the injection in the striatum a lesion developed. In the presence of AMPA (50 nmol) administered intrastriatally, GYKI 52466 (75 mg/kg i.p.) was able to make the radioactive signal of [3H]girisopam reappear. The volume of AMPA induced neuronal damage in the striatum and the extent of gliosis was reduced. These data provide evidence for the neuroprotective effect of GYKI 52466, and suggest a potential therapeutic value in some neurological disorders.

Sonochemical and thermal redox reactions of triphenylmethane and triphenylmethyl carbinol in nitrobenzene.

The reaction of triphenylmethane and triphenylcarbinol with nitrobenzene under thermal or ultrasonic activation was studied. It was shown beyond doubt that the thermal reaction of the aforementioned systems at 210 degrees C occurs through electron transfer. The sonochemical reactions occur at 40 degrees C, although slowly, while heating at the same temperature leaves the system unchanged. Electron transfers are also involved but an unexpected reductive process was evident.

[Total proximal reconstruction of chronic aortic dissection in patients with Marfan syndrome]. / Marfan-kóros betegeknél észlelt krónikus aorta dissectio teljes proximalis korrekciója.

Authors present two patients suffering from Marfan syndrome. Asymptomatically developed serious cardiovascular complications being characteristic of the syndrome itself were revealed at both cases. Type "A" aortic dissection was found at the first, and type "B" aortic dissection involving even the arch as well revealed at the other patient. They were operated on an elective base. Total proximal aortic reconstructions (aortic root-ascending aorta-arch) were performed under deep hypothermia using total circulatory arrest (35 and 87 min). Both patients are doing well without complaints 3-4 months following the surgical interventions. Control angiographic imagination has found normal anatomic conditions at one of the patients. Anastomosis stenosis at the borderline of the arch and descending aorta was revealed at the other case which should be necessary to operate at an later occasion.

[Transesophageal echocardiography from the surgical viewpoint]. / Transösophageale Echokardiographie aus chirurgischer Sicht.

Following the development of new techniques in echocardiography and especially of Doppler color flow imaging, a new dimension of cardiac surgery has been brought about. The use of transesophageal probes facilitates routine surgery to be performed without interferences and, also, comparability between repeated ultrasonic measurements. Originally, echocardiography was mainly applied for quality control by comparing pre- and postoperative echocardiograms. Now it is equally important in perioperative strategy planning guiding the surgeon's decision throughout the operation as well as in cardiac emergencies. Using intraoperative echocardiography routinely in cardiac surgery establishes a more and more close cooperation between surgeons, cardiologists, and anesthesiologists. In order to evaluate the clinical relevance of echo findings, they have to be repeatedly correlated to surgical realities and to long term results of clinical outcome.

Early and late hormonal modulation of cholinergic maturation in culture of embryonic mesencephali.

Dissociated cells from 13- and 17-day-old embryonic rat mesencephali have grown in primary cultures in order to compare the early and late influences of different agents--insulin, dexamethasone and nerve growth factor (NGF)--on the expression of cholinergic maturation process. We have studied cholin acetyltransferase (ChAT) activity, which is regarded as a specific marker for cholinergic function of the brain, and a widely used differentiation marker, the acetyl-cholinesterase (AchE) enzyme. Biochemical maturation of increasing specific activity of ChAT in both younger and older cells was taken into consideration. During cultivation the AchE activity was slightly increased in younger cells, but a dramatic decrease could be noted in older ones. Insulin in concentration from 10 to 27 micrograms mL-1 causes a significant inhibition in ChAT activity in comparison with the enzyme activity measured in control cultures (insulin ranging from 1 to 100 ng), independently of embryos age. This polypeptide hormone is able to enhance AchE activity in the cultured cells, especially in older ones. With continuous treatment of the culture with dexamethasone, a synthetic glucocorticoid, the ChAT activity in younger cells reaches a maximum curve by day 9 (nine). At this time the AchE activity shows a slighter, no significant increase than at any other time during cultivation. In cell cultures taken from 17-day-old embryos however dexamethasone treatment evoked a significant decrease in ChAT activity with a concomitant increase of AchE activity which was compared to insulin treatment. In spite of the fact that the NGF is able to enhance the ChAT activity, no significant alteration in AchE activity can be measured in younger cell cultures. These results suggest an uneven expression of the enzymes in embryonic rat mesencephali in the presence of above agents depending on the age of cells.

[Experience with the surgical management of constrictive pericarditis]. / Tapasztalataink a constrictiv pericarditis sebészi kezelésében.

61 patients were operated on for constrictive pericarditis at the Cardiovascular Surgical Clinic of Semmelweis Medical University in the last 33 years. The average hospital mortality of the surgical pericardiectomy was 4.9%. The final conclusions of this retrospective and follow up study are as follows: pericardiectomy is the method of choice in the treatment of constrictive pericarditis, since it does not has any therapeutic alternative, its hospital mortality is low and it results excellent early and late postoperative functional effects.

Biological valve prosthesis replacement--experiences and considerations.

Between 1976 and 1991. 1.017 tissue valve prostheses were implanted in 801 patients. During the same period 1876 mechanical valve prostheses were replaced. The hospital mortality was 8.1%. Till 1991 230 bioprostheses (22.6%) in the case of 166 patients (20.7%) had to be removed and replaced by other valve prostheses. There are no significant differences concerning the mortality between the first (8.1%) and the second operations (9.1%), and the durability of the various types of bioprostheses used, however, calcification, degeneration and other complications occurred more frequently and earlier in the case of mitral (24.5%) than in aortic (18.9%) bioprostheses, and in younger patients than in the older ones, as well. The mean age of patients was 46 years at the time of the first and 49 years at the time of the second operation. The incidence of reoperations was the highest in the seventh year after the first surgical intervention. In general, one size smaller prostheses were used in valve replacements after the removal of the first bioprostheses.

Hormonal modulation of neuronal cells behaviour in vitro.

In this study we have investigated the effect of insulin and/or of nerve growth factor (NGF) on enzyme activities of cholinergic neurotransmission, in cultured embryonic rat mesencephali. Our data show that choline-O-acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity display a prominent change in the embryonic brain tissues as a function of time in vitro. The change depends on the age of embryos from which the brain cell cultures have been set up. Namely, ChAT activity increases in the cultures taken from 13-17-day-old embryos as a function of time in vitro. AChE activity shows a striking decrease if the cultures have been set up from the older embryos (17-day-old), while AChE activity increases in the cultures prepared from 13-day-old embryos continuously. Insulin (amount ranging 10-27 micrograms/ml) causes a significant inhibition in the ChAT activity in comparison with the increased enzyme activity measured in control cultures (insulin ranging from 1 to 100 ng). AChE activity of 13-day-old embryos was not influenced by insulin (20-27 micrograms/ml) but the same amount of insulin prevents the decrease of AChE activity in cultured brain cells originating from 17-day-old-embryos. Biochemical studies of NGF treated cultures (30 ng/ml) revealed that nerve growth factor resulted in 5-12-fold increase in specific activity of the cholinergic enzyme, choline acetyltransferase (ChAT). NGF did not influence the AChE activity in cultured brain cells (13-17-day-old).

45Ca2+ uptake and peptide hormones secretion in the presence of excess Mg2+ content.

Studies have been performed on the relationship between PRL and GH production and the 45Ca2+ influx in high magnesium content in vitro. The obtained data show that an elevated magnesium concentration in Krebs-Ringer solution is capable of inhibiting some hormonal function of the pituitary gland. It has been found, that PRL and GH released into the media in normal KRB solution revealed nearly two times higher concentration than in the presence of high Mg2+. Instead the cellular iPRL and iGH did not show any significant differences in control and in treated cultures. The incorporation of 4.5-3H-leucine into the prolactin and growth hormone demonstrate a significant decrease in the presence of high Mg2+ indicating that the ion is able to inhibit the secretion of newly synthesized PRL an GH. High concentration of Mg2+ abolished either the stimulation effect of releasing hormones on calcium uptake.