Propofol versus sevoflurane anaesthesia: effect on cognitive decline and event-related potentials.

Postoperative cognitive dysfunction (POCD) is diagnosed in up to 30% patients after anaesthesia. The causative role of anaesthetic toxicity remains unclear. Using clinical tests, no clear-cut differences have been observed between anaesthetics so far. The aim of this trial was to compare the incidence of POCD diagnosed by a battery of neuropsychologic tests after propofol and sevoflurane anaesthesia. Secondary goal was to examine possible relationship between POCD positivity and changes in auditory event-related potentials (ERPs). Sixty patients undergoing lumbar discectomy were prospectively randomized to receive depth-controlled sevoflurane (SEVO) or propofol (PROP) based anaesthesia. The neuropsychological examination and auditory event-related potentials (N1, P3a and P3b components) recording was performed preoperatively and on days 1, 6 and 42 after surgery. POCD was defined as a decline of more than one standard deviation in three or more tests. In 43 patients (20 in PROP and 23 in SEVO group) all selected tests were performed and used for the evaluation. POCD was present in 48%/60%, 18%/20% and 17%/11% (SEVO/PROP) of patients on days 1, 6 and 42 after surgery, with no significant intergroup difference. Among neuropsychologic tests, the most significant decline was observed in Semantic Verbal Fluency and Letter-Number Sequencing Test scores, congruently in both groups on days 1 and 6, with full recovery on the last control. Transient deteriorations in other tests were observed as well. No association of POCD positivity and ERPs changes was found, although long-term modifications of P3a and P3b components were observed, mainly in SEVO group. In our study, sevoflurane and propofol anaesthesia was associated with the similar incidence of POCD. Cognitive decline, mainly affecting executive functions, was temporary in most of the patients. Prolonged ERPs alterations after the anaesthesia seem not to have any relationship with the impairment registered by the neuropsychological examination and may represent subclinical changes.

Fluid management guided by a continuous non-invasive arterial pressure device is associated with decreased postoperative morbidity after total knee and hip replacement.

BACKGROUND: The use of goal directed fluid protocols in intermediate risk patients undergoing hip or knee replacement was studied in few trials using invasive monitoring. For this reason we have implemented two different fluid management protocols, both based on a novel totally non-invasive arterial pressure monitoring device and compared them to the standard (no-protocol) treatment applied before the transition in our academic institution. METHODS: Three treatment groups were compared in this prospective study: the observational (CONTROL, N = 40) group before adoption of fluid protocols and two randomized groups after the transition to protocol fluid management with the use of the continuous non-invasive blood pressure monitoring (CNAP®) device. In the PRESSURE group (N = 40) standard variables were used for restrictive fluid therapy. Goal directed fluid therapy using pulse pressure variation was used in the GDFT arm (N = 40). The influence on the rate of postoperative complications, on the hospital length of stay and other parameters was assessed. RESULTS: Both protocols were associated with decreased fluid administration and maintained hemodynamic stability. Reduced rate of postoperative infection and organ complications (22 (55 %) vs. 33 (83 %) patients; p = 0.016; relative risk 0.67 (0.49-0.91)) was observed in the GDFT group compared to CONTROL. Lower number of patients receiving transfusion (4 (10 %) in GDFT vs. 17 (43 %) in CONTROL; p = 0.005) might contribute to this observation. No significant differences were observed in other end-points. CONCLUSION: In our study, the use of the fluid protocol based on pulse pressure variation assessed using continuous non-invasive arterial pressure measurement seems to be associated with a reduction in postoperative complications and transfusion needs as compared to standard no-protocol treatment. TRIAL REGISTRATION: ACTRN12612001014842.

Continuous non-invasive monitoring improves blood pressure stability in upright position: randomized controlled trial.

Intermittent blood pressure (BP) monitoring is the standard-of-care during low and intermediate risk anaesthesia, yet it could lead to delayed recognition of BP fluctuations. Perioperative hypotension is known to be associated with postoperative complications. Continuous, non-invasive methods for BP monitoring have been developed recently. We have tested a novel non-invasive, continuous monitor (using the volume clamp method) to assist with maintaining BP in safe ranges for patients undergoing surgery in a beach chair position. Forty adult patients undergoing thyroid gland surgery in an upright position were included in this prospective randomised controlled trial. Patients were equally allocated to the group with continuous monitoring of BP using the CNAP® Monitor and to the control group managed using an intermittent oscillometric BP cuff. The absolute and proportional time spent outside the range of ±20% of the target BP along with other hemodynamic and clinical parameters were evaluated. The continuous monitoring decreased the anaesthesia time spent below -20% pressure range [absolute: 12 min (4-20) vs. 27 min (16-34); p=0.001; relative to procedure length: 14% (7-20) vs. 33.5% (17.5-53); p=0.003]. No significant differences were observed in postoperative morbidity or in hospital length of stay. Continuous non-invasive BP monitoring via the CNAP® Monitor allows for better BP management in patients undergoing surgery in a beach chair position. In our randomised trial the time spent in hypotension was significantly shorter using continuous monitoring.

Cost analysis of the stroke volume variation guided perioperative hemodynamic optimization - an economic evaluation of the SVVOPT trial results.

BACKGROUND: Perioperative goal directed therapy (GDT) can substantially improve the outcomes of high risk surgical patients as shown by many clinical studies. However, the approach needs initial investment and can increase the already very high staff workload. These economic imperatives may be at least partly responsible for weak adherence to the GDT concept. A few models are available for the evaluation of GDT cost-effectiveness, but studies of real economic data based on a recent clinical trial are lacking. In order to address this we have performed a retrospective analysis of the data from the "Intraoperative fluid optimization using stroke volume variation in high risk surgical patients" trial (ISRCTN95085011). METHODS: The health-care payers perspective was used in order to evaluate the perioperative hemodynamic optimization costs. Hospital invoices from all patients included in the trial were extracted. A direct comparison between the study (GDT, N = 60) and control (N = 60) groups was performed. A cost tree was constructed and major cost drivers evaluated. RESULTS: The trial showed a significant improvement in clinical outcomes for GDT treated patients. The mean cost per patient were lower in the GDT group 2877 ± 2336€ vs. 3371 ± 3238€ in controls, but without reaching a statistical significance (p = 0.596). The mean cost of all items except for intraoperative monitoring and infusions were lower for GDT than control but due to the high variability they all failed to reach statistical significance. Those costs associated with clinical care (68 ± 177€ vs. 212 ± 593€; p = 0.023) and ward stay costs (213 ± 108€ vs. 349 ± 467€; p = 0.082) were the most important differences in favour of the GDT group. CONCLUSIONS: Intraoperative fluid optimization with the use of stroke volume variation and Vigileo/FloTrac system showed not only a substantial improvement of morbidity, but was associated with an economic benefit. The cost-savings observed in the overall costs of postoperative care trend to offset the investment needed to run the GDT strategy and intraoperative monitoring. TRIAL REGISTRATION: ISRCTN95085011.

Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial.

INTRODUCTION: Meropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration of pathogens. The goal of this study was to compare clinical and bacteriological efficacy of continuous meropenem infusion versus bolus administration in critically ill patients with severe infection, and to evaluate the safety of both dosing regimens. METHODS: Patients admitted to the interdisciplinary Intensive Care Unit (ICU) who suffered from severe infections and received meropenem were randomized either in the Infusion group (n = 120) or in the Bolus group (n = 120). Patients in the Infusion group received a loading dose of 2 g of meropenem followed by a continuous infusion of 4 g of meropenem over 24 hours. Patients in the Bolus group were given 2 g of meropenem over 30 minutes every 8 hours. Clinical and microbiological outcome, safety, meropenem-related length of ICU and hospital stay, meropenem-related length of mechanical ventilation, duration of meropenem treatment, total dose of meropenem, and ICU and in-hospital mortality were assessed. RESULTS: Clinical cure at the end of meropenem therapy was comparable between both groups (83.0% patients in the Infusion vs. 75.0% patients in the Bolus group; P = 0.180). Microbiological success rate was higher in the Infusion group as opposed to the Bolus group (90.6% vs. 78.4%; P = 0.020). Multivariate logistic regression identified continuous administration of meropenem as an independent predictor of microbiological success (OR = 2.977; 95% CI = 1.050 to 8.443; P = 0.040). Meropenem-related ICU stay was shorter in the Infusion group compared to the Bolus group (10 (7 to 14) days vs. 12 (7 to 19) days; P = 0.044) as well as shorter duration of meropenem therapy (7 (6 to 8) days vs. 8 (7 to 10) days; P = 0.035) and lower total dose of meropenem (24 (21 to 32) grams vs. 48 (42 to 60) grams; P < 0.0001). No severe adverse events related to meropenem administration in either group were observed. CONCLUSIONS: Continuous infusion of meropenem is safe and, in comparison with higher intermittent dosage, provides equal clinical outcome, generates superior bacteriological efficacy and offers encouraging alternative of antimicrobial therapy in critically ill patients.

The impact of general versus local anesthesia on early subclinical cognitive function following carotid endarterectomy evaluated using P3 event-related potentials.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is detected in 25% of patients undergoing carotid endarterectomy (CEA). The mechanism of POCD is poorly understood, but it is believed that general anesthesia (GA) itself may contribute significantly to POCD. The aim of our prospective study was to compare, with the aid of event-related potentials, the impact of general anesthesia (GA) and local anesthesia (LA) on POCD in patients undergoing CEA. METHODS: Sixty patients were included in this study and were divided into two groups: CEA was performed in 30 patients placed under GA (total intravenous anesthesia), herein the GA group, while 30 patients underwent CEA under LA (cervical plexus block), herein LA group. Cognitive outcome was assessed with the use of auditory event-related potentials (ERPs), P3 response. The measurements were taken before surgery (pre-op) and on the first (1.post-op) and the sixth postoperative days (6.post-op). RESULTS: Preoperative cognitive functions did not differ significantly between the two groups. A significant decrease in P3 amplitude was found on the first postoperative day (1.post-op) in the GA group (p = 0.0005), but normalization of P3 amplitude was detected at the second postoperative measurement (6.post-op). The patients operated on under local anesthesia (LA group) showed stable P3 amplitudes in all three measurements. No significant changes in P3 latencies were observed in either group. There were no significant differences between the two groups regarding demographic characteristics, preoperative and postoperative clinical condition, percentage significance of carotid artery stenosis, duration of carotid cross-clamping or in the frequency of shunt use (zero frequency for both groups). CONCLUSIONS: Our study showed that general anesthesia, used for patients undergoing CEA, negatively influenced cognitive function during the immediate period after surgery (the first postoperative day). However, by the sixth postoperative day, this cognitive impairment was no longer being detected. POCD occurring shortly after carotid endarterectomy is the result of general anesthesia, which is probably an independent evoking factor in itself. The cognitive deficit recorded only during the immediate postoperative period, is not a negative effect of GA but merely a side-effect and thus GA should not be considered inferior to LA for use during CEA.

Intraoperative fluid optimization using stroke volume variation in high risk surgical patients: results of prospective randomized study.

INTRODUCTION: Stroke volume variation (SVV) is a good and easily obtainable predictor of fluid responsiveness, which can be used to guide fluid therapy in mechanically ventilated patients. During major abdominal surgery, inappropriate fluid management may result in occult organ hypoperfusion or fluid overload in patients with compromised cardiovascular reserves and thus increase postoperative morbidity. The aim of our study was to evaluate the influence of SVV guided fluid optimization on organ functions and postoperative morbidity in high risk patients undergoing major abdominal surgery. METHODS: Patients undergoing elective intraabdominal surgery were randomly assigned to a Control group (n = 60) with routine intraoperative care and a Vigileo group (n = 60), where fluid management was guided by SVV (Vigileo/FloTrac system). The aim was to maintain the SVV below 10% using colloid boluses of 3 ml/kg. The laboratory parameters of organ hypoperfusion in perioperative period, the number of infectious and organ complications on day 30 after the operation, and the hospital and ICU length of stay and mortality were evaluated. The local ethics committee approved the study. RESULTS: The patients in the Vigileo group received more colloid (1425 ml [1000-1500] vs. 1000 ml [540-1250]; P = 0.0028) intraoperatively and a lower number of hypotensive events were observed (2[1-2] Vigileo vs. 3.5[2-6] in Control; P = 0.0001). Lactate levels at the end of surgery were lower in Vigileo (1.78 +/- 0.83 mmol/l vs. 2.25 +/- 1.12 mmol/l; P = 0.0252). Fewer Vigileo patients developed complications (18 (30%) vs. 35 (58.3%) patients; P = 0.0033) and the overall number of complications was also reduced (34 vs. 77 complications in Vigileo and Control respectively; P = 0.0066). A difference in hospital length of stay was found only in per protocol analysis of patients receiving optimization (9 [8-12] vs. 10 [8-19] days; P = 0.0421). No difference in mortality (1 (1.7%) vs. 2 (3.3%); P = 1.0) and ICU length of stay (3 [2-5] vs. 3 [0.5-5]; P = 0.789) was found. CONCLUSIONS: In this study, fluid optimization guided by SVV during major abdominal surgery is associated with better intraoperative hemodynamic stability, decrease in serum lactate at the end of surgery and lower incidence of postoperative organ complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95085011.

Esophageal Doppler-guided fluid management decreases blood lactate levels in multiple-trauma patients: a randomized controlled trial.

INTRODUCTION: Esophageal Doppler was confirmed as a useful non-invasive tool for management of fluid replacement in elective surgery. The aim of this study was to assess the effect of early optimization of intravascular volume using esophageal Doppler on blood lactate levels and organ dysfunction development in comparison with standard hemodynamic management in multiple-trauma patients. METHODS: This was a randomized controlled trial. Multiple-trauma patients with blood loss of more than 2,000 ml admitted to the intensive care unit (ICU) were randomly assigned to the protocol group with esophageal Doppler monitoring and to the control group. Fluid resuscitation in the Doppler group was guided for the first 12 hours of ICU stay according to the protocol based on data obtained by esophageal Doppler, whereas control patients were managed conventionally. Blood lactate levels and organ dysfunction during ICU stay were evaluated. RESULTS: Eighty patients were randomly assigned to Doppler and 82 patients to control treatment. The Doppler group received more intravenous colloid during the first 12 hours of ICU stay (1,667 +/- 426 ml versus 682 +/- 322 ml; p < 0.0001), and blood lactate levels in the Doppler group were lower after 12 and 24 hours of treatment than in the control group (2.92 +/- 0.54 mmol/l versus 3.23 +/- 0.54 mmol/l [p = 0.0003] and 1.99 +/- 0.44 mmol/l versus 2.37 +/- 0.58 mmol/l [p < 0.0001], respectively). No difference in organ dysfunction between the groups was found. Fewer patients in the Doppler group developed infectious complications (15 [18.8%] versus 28 [34.1%]; relative risk = 0.5491; 95% confidence interval = 0.3180 to 0.9482; p = 0.032). ICU stay in the Doppler group was reduced from a median of 8.5 days (interquartile range [IQR] 6 to16) to 7 days (IQR 6 to 11) (p = 0.031), and hospital stay was decreased from a median of 17.5 days (IQR 11 to 29) to 14 days (IQR 8.25 to 21) (p = 0.045). No significant difference in ICU and hospital mortalities between the groups was found. CONCLUSION: Optimization of intravascular volume using esophageal Doppler in multiple-trauma patients is associated with a decrease of blood lactate levels, a lower incidence of infectious complications, and a reduced duration of ICU and hospital stays.

Acquired angioedema and Helicobacter pylori infection in a child.

UNLABELLED: We describe a 10-year-old boy with acquired Helicobacter pylori infection and simultaneous angioedema which is a rare but life-threatening condition. Our patient was hospitalised with generalised angioedema and severe circulatory shock due to extreme loss of fluids and proteins into interstitial tissues (weight gain 10 kg within 2 days, extreme haemoconcentration--haemoglobin 206 g/l, haematocrit 0.570, leucocytosis 18,300 /microl, high lactate 13.8 mmol/l) and simultaneous failure of the complement system (C3 <0.16 g/l, C4 <0.13 g/l, CH50 45 U/ml, i.e. 50% of normal value, C1 inhibitor 0.21 g/l at the lower limit). All possible known causes of angioedema were excluded (infection, allergy, auto-immune disease, NSAIDs, lymphoproliferative disease) except for the simultaneous H. pylori infection which was proven serologically and histologically. Eradication therapy led to a complete remission of the H. pylori infection. An absence of angioedema and the restoration of the complement system was later observed. To the best of our knowledge, no similar case report of a child has yet been published. CONCLUSION: Helicobacter pylori infection should be considered in the development of angioedema in childhood.