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.

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.

[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.

Acetylcholinesterase (AchE) activity of lymphocytes in chronic lymphoid leukemia (CLL).

The specific AchE (EC 3.1.1.7) activity of lymphocytes from the peripheral blood of normal donors was determined. On Leukopak filter the isolated T lymphocytes showed activity, whereas in stepwise Percoll gradient, population TLD displayed enzyme activity. The THD and B cells were inactive. [Szelényi J. G., Bartha E. & Hollán S. R. (1982) Br. J. Haemat. 50, 241]. A mixed cell population derived from CLL patients had significantly lower enzyme activity than normal. With the progress of B-cell proliferation AchE activity decreased in parallel with the number of T cells. The sp. act. of TLD population isolated from CLL patients was the same as that of normal donors whereas their B cells were inactive.

Altered lymphocyte acetylcholinesterase activity in patients with senile dementia.

Reductions in the acetylcholinesterase (AChE) activity of certain brain areas in patients with senile dementia of Alzheimer type (SDAT) have been found to correlate with the severity of the disease, suggesting a central cholinergic lesion. Since AChE is expressed on the surface of various blood cells too, the AChE activity of lymphocytes and erythrocytes was determined to test the possibility whether the cholinergic lesion is also reflected on these readily available cells. The AChE activity of lymphocytes in SDAT and in alcoholic dementia (AD) were significantly lower as compared to those of the age-matched healthy volunteers. In contrast, there was no significant difference in the activity of lymphocyte AChE between age-matched healthy controls and patients with multi-infarct dementia of vascular origin (MID). No changes could be demonstrated in the erythrocyte AChE activities of the patients studied, and the age-matched healthy individuals, when comparing them to the healthy blood donors. The AChE activity of lymphocytes may thus be a useful marker to follow the alterations in the metabolism of acetylcholine (ACh) in the central nervous system (CNS) of different types of dementia.

Molecular form of human lymphocyte membrane-bound acetylcholinesterase.

The membrane-bound acetylcholinesterase (AchE) from human peripheral blood lymphocyte gives only one symmetrical peak on sucrose density gradient centrifugation in the presence of Triton X-100 detergent, with the calculated sedimentation coefficient of 6.5 S. However, this dimeric form of AchE was converted to a monomeric 3.8 S form when treated with 2-mercaptoethanol and iodoacetic acid. The results are consistent with studies which have shown by sodium dodecyl sulfate gel electrophoresis that the enzyme is built up of two identical monomers inter-linked by disulfide bond(s). Under reducing conditions, revealed a single species of 70,000 molecular weight, whereas under non-reducing conditions, another species of 140,000 molecular weight of the AchE was found. Polyacrylamide gel electrophoresis indicated a single band with AchE activity in the presence of Triton X-100. In contrast, in the absence of the same detergent multiple band pattern could be observed. These results suggest that membrane-bound AchE enzyme is present in homogenous dimeric form on human lymphocyte membrane.

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.

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.

[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.

[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.

[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.

[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.

[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.

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.