The influence of the SARS-CoV-2 lockdown on patients with inflammatory rheumatic diseases on their adherence to immunomodulatory medication: a cross sectional study over 3 months in Germany.

OBJECTIVES: To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-month lockdown in Germany. METHODS: From 16th March until 15th June 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. CONCLUSION: The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behaviour with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendations of the German Society of Rheumatology were well received, supporting the well-established physician-patient relationship in times of a crisis.

[A cross sectional study on patients with inflammatory rheumatic diseases in terms of their compliance to their immunsuppressive medication during COVID-19 pandemic]. / Einstellung von Patienten mit entzündlich-rheumatischen Erkrankungen zur immunsuppressiven Therapie im Rahmen der COVID-19 Pandemie ­ eine Situationsanalyse.

The current COVID-19 pandemic inherits an unprecedented challenge for the treating rheumatologists. On the one hand, antirheumatic drugs can increase the risk of infection and potentially deteriorate the course of an infection. On the other hand, an active inflammatory rheumatic disease can also increase the risk for an infection. In the recommendations of the German Society for Rheumatology (www.dgrh.de), it is recommended that our patients continue the antirheumatic therapy to maintain remission or low state of activity despite the pandemic. In this study, patients with inflammatory rheumatic disease were asked in the first weeks of the pandemic on their opinion of their immunomodulating therapy. The result shows that over 90% of the patients followed the recommendation of the rheumatologist to continue the antirheumatic therapy, and only a small percentage of the patients terminated the therapy on their own. This result was independent of the individual anti-rheumatic therapy. Taken together, the results of this study illustrate not only the trustful patient-physician partnership in a threatening situation but also the high impact of state-of-the art recommendations by the respective scientific society.

[Serotonin transporter gene and stress reactivity in unipolar depression. Role of the HPA system as endophenotype of the SLC6A4 gene]. / Serotonintransportergen und Stressreagibilität bei unipolarer Depression. Rolle des HPA-Systems als Endophänotyp des Gens SLC6A4.

BACKGROUND: A length polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with both depression and hypothalamic-pituitary-adrenal (HPA) system activity. A dysregulation of the HPA system is considered to be a candidate endophenotype of depression. The objective of the present study was an investigation of a possible gene-endophenotype-interaction between 5-HTTLPR and HPA system activity in a sample of inpatients with major depression. MATERIALS AND METHODS: A total of 237 inpatients with major depression were genotyped for 5-HTTLPR and participated in a combined dexamethasone-corticotropin-releasing hormone test (Dex-CRH test) as well as using the Hamilton score (Hamilton rating scale for depression) to determine the severity of the psychopathology. RESULTS: Patients with the ss-genotype showed a significantly higher HPA -system activity in comparison to patients with the lI-genotype, but no association between 5-HTTLPR and the severity of psychopathology could be detected. CONCLUSIONS: The results of the current study demonstrate an influence of 5-HTTLPR on dysregulation of the HPA system in patients with major depression and support the hypothesis that 5-HTTLPR- and HPA-system-interaction constitutes an important component in the pathogenesis of depression.

Delay of transfer from the intensive care unit: a prospective observational analysis on economic effects of delayed in-house transfer.

BACKGROUND: Intensive care unit (ICU) capacity is a scant and precious resource in hospitals. Therefore, an optimal occupancy rate as well as detailed occupation planning is of great importance. Most literature deals with admission to the ICU, while only few discuss discharge from the ICU. Specifically, a delay of transfer from the ICU can cause a shortness of beds, jeopardize urgent patient treatment and lead to a decrease in treatment quality as well as economic downsides. This study examined the incidence, costs and reasons for delayed discharge from the ICU and analyzed the influence of the department the patient was admitted to. METHODS: Over the course of 12 months, the discharges of all 1643 patients of two surgical intensive care units of a large academic medical center were analyzed. Delay in minutes and reasons were recorded and translated into financial figures. A univariate logistic regression model was developed to evaluate the impact of length of stay at the ICU, age, gender, subspecialty and specific ICU on the delay of transfer. In a next step, significant factors of the univariate logistic regression were incorporated into a multivariate regression model. RESULTS: In 326 out of 1312 patients ready for discharge (24.8%), the transfer to the floor was delayed. Time of delay for all patients added up to a total of 265,691 min in 1 year. The application of the internal cost allocation, in which 1 min corresponds to 0.75 Euro cents, led to costs of 199,268 Euros (~ $240,000) for the study period. In 91.7% of the cases, the reason for the delay was the lack of an available or appropriate bed on the regular ward. Multivariate regression analysis revealed that the type of department the patient is admitted to poses a significantly influencing factor for delayed discharge from the ICU. CONCLUSION: Delay in discharge from the ICU is a common problem of economic relevance. The main reason is a lack of appropriate floor beds. Patients from certain specific departments are at a higher risk to be discharged with delay. A solution to this problem lies in the focus on the downstream units. A proper use of the scarce resources is to be pursued because of ethical as well as economic reasons in an increasingly aging population.

Right frontal hypergyria differentiation in affected and unaffected siblings from families multiply affected with schizophrenia: a morphometric mri study.

OBJECTIVE: The authors used magnetic resonance imaging to corroborate the postmortem finding of right frontal hypergyria associated with schizophrenia. METHOD: Twelve affected-unaffected sibling pairs from families multiply affected with schizophrenia were studied. Bilateral measurement of the gyrification index, the ratio of the inner and outer surface contours, was performed on three different slices of the prefrontal region. RESULTS: The mean gyrification index on the right side was significantly higher in siblings with schizophrenia or schizoaffective disorder than in the unaffected siblings. CONCLUSIONS: In this family cohort study, the postmortem finding of right-sided hypergyria in subjects with schizophrenia was replicated in vivo with magnetic resonance imaging. This observation provides further support for a neurodevelopmental mechanism in the pathogenesis of schizophrenia.

Disturbed gyrification of the prefrontal region in male schizophrenic patients: A morphometric postmortem study.

OBJECTIVE: The goal was to test the hypothesis that abnormalities of gyrification are present in the prefrontal region of postmortem brains from schizophrenic patients. METHOD: The authors compared the prefrontal regions in brains from 24 schizophrenic patients and 24 normal comparison subjects. The gyrification index, the ratio of inner and outer surface contours, was measured bilaterally in three different slices from each brain. Area measurements of gray and white matter were studied separately by planimetric analysis in the same sections. In addition, a gray-to-white-matter ratio and an asymmetry coefficient were computed. RESULTS: The mean gyrification index on the right side was significantly higher in the male schizophrenic patients than in the comparison men. The gyrification index of the female patients was not significantly different from that of the female comparison subjects. Analysis of area measurements revealed no significant differences. CONCLUSIONS: As gyrification is an ontogenetic stable feature unaffected by atrophic processes during aging, the gyrification abnormalities of the prefrontal region provide further evidence of the importance of a neurodevelopmental mechanism in the etiology of schizophrenia, at least in males.

Synthesis and pharmacological activity of a series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones, a novel class of potent cognition enhancers.

A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones were synthesized. These bicylic derivatives contain both the 2-pyrrolidinone and 4-imidazolidinone nuclei, already recognized as important for cognition enhancing activity. In addition, these structures maintain the backbone of piracetam and oxiracetam with the acetamide side chain restricted in a folded conformation. Their ability to reverse scopolamine-induced amnesia was assessed in a one trial, step-through, passive avoidance paradigm. The main features observed are a potent antiamnestic activity after ip administration (minimal effective dose being between 0.3 and 1 mg/kg ip for most compounds), the presence of a bell-shaped dose-response curve and, generally, a reduction of biological activity after po administration. However, the unsubstituted compound (15, dimiracetam) shows no evidence of a bell-shaped dose-response curve and completely retains activity when given orally, being 10-30 times more potent than the reference drug oxiracetam.

Efficacy of pressure support ventilation dependent on extravascular lung water.

Continuous positive-pressure ventilation and PSV were compared prospectively in patients at a surgical intensive care unit. All patients suffered from mild to moderate ARI (PaO2/FIO2 of 125 to 350 mm Hg). The patients were randomly assigned to a PSV group (n = 28) or a control group with continued CPPV (n = 27). The usual hemodynamic and oxygenation variables, ITBV, and extravascular lung water (ETV) were assessed before and six hours after switching to PSV. The changes (d) of PaO2/FIO2, RI, and P(A-a)O2 were used for evaluation of the effect of PSV. Significant correlations were found between the ETV(CPPV) and dPaO2/FIO2 (r = -0.672), ETV(CPPV) and dRI (r = 0.722), and ETV(CPPV) and dP(A-a)O2 (r = 0.601), which led to the conclusion that the level of ETV determined the efficacy of PSV. In the subgroup with ETV less than 11 ml/kg (n = 15), PSV significantly improved PaO2/FIO2 (248 to 286 mm Hg), RI (1.55 to 1.22), ITBV (801 to 888 ml/m2), cardiac index (4.21 to 4.76 L/min.m2), stroke index (42.2 to 48.1 ml/m2), and oxygen delivery (735 to 833 ml/min.m2). In the subgroup with ETV greater than 11 ml/kg (n = 13), PSV caused a significant deterioration of PaO2/FIO2, RI, and intrapulmonary shunt. It is concluded that in patients with moderate ARI in whom ETV is almost normal, PSV is superior to CPPV, and the efficacy of PSV is independent of the level of oxygenation during CPPV.

Hemodynamic monitoring by double-indicator dilution technique in patients after orthotopic heart transplantation.

STUDY OBJECTIVES: A transpulmonary thermal-dye dilution (TDD) technique using cold indocyanine green dye was utilized to monitor cardiac index (CI) and preload in patients after heart transplantation. Preload, determined by intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI), was compared to central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) and was correlated with stroke volume index (SVI). DESIGN: Prospective study. SETTING: Cardiac surgery ICU at a university hospital. PATIENTS: Forty patients (34 men, 6 women) with a mean (+/- SD) age of 54.4+/-8.5 years after orthotopic heart transplantation. MEASUREMENTS AND RESULTS: CI and preload measurements were performed with TDD and pulmonary artery catheters in the ICU at 3, 6, 12, 24, 36, 48, and 72 h postoperatively. The femoral artery CI was compared with the pulmonary artery CI. Changes in the ITBVI, GEDVI, CVP, and PAOP were correlated with changes in the SVI. No difference was found between the femoral and pulmonary arterial CIs (r = 0.98 [bias, 0.35 L/min/m(2)]; p<0.01). There was no statistically significant correlation between changes in the SVI and changes in CVP (r = -0.23,) and PAOP (r = -0.06). However, the ITBVI (r = 0.65; p<0.01) and the GEDVI (r = 0.73; p<0.01) were significantly correlated to changes in the SVI. Changes in the same direction occurred between the SVI and the GEDVI as well as between the SVI and the ITBVI in 76.3% and 71.9% of patients, respectively, while CVP and PAOP also changed in the same direction as SVI in only 35.1% and 36.9% of patients, respectively. CONCLUSION: ITBVI and GEDVI are more reliable preload parameters than CVP and PAOP. Even in denervated hearts, ITBVI and GEDVI show significant correlations with SVI. The transpulmonary indicator dilution technique is promising and should be investigated further.

Disturbed planum temporale asymmetry in schizophrenia. A quantitative post-mortem study.

The planum temporale of the temporal cortex was investigated post-mortem in 24 schizophrenic patients and 24 age- and sex-matched control subjects. Schizophrenic patients demonstrated a 20% volume reduction of the left planum temporale (p = 0.032), whereas on the right side, there was a trend for increase in male schizophrenics (+22%, p = 0.17), while in female patients the volume was moderately decreased (-6%, p = 0.74). The mean anterior-posterior diameter of the planum temporale was significantly reduced in the left hemisphere (-20%, p = 0.008), but unchanged on the right side. The asymmetry coefficients (Galaburda et al. (1987) Neuropsychologia 25, 853-868) for the planum temporale cortex volume (p = 0.02) and anterior-posterior diameter (p = 0.002) but not for mean area (p = 0.61) were significantly different between schizophrenics and control subjects. These data support the idea of disturbed cerebral laterality in schizophrenia. The implications of methodology and patient samples are discussed.

Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study.

The sylvian fissure is known to be one of the most asymmetric structures of the human brain. Sylvian fissure length was measured in post-mortem brains of 35 schizophrenic patients and 33 matched non psychiatric control subjects. The schizophrenics showed a significantly reduced length of the left sylvian fissure (-16%, p less than 0.0001) compared to the control subjects, while the right sylvian fissure length was unchanged. Sylvian fissure asymmetry (left/right ratio) was more reduced in male schizophrenics (-24%, p less than 0.001) than in female patients (-16%, p less than 0.03). This finding is consistent with several post-mortem and MRI studies showing left temporal lobe pathology in a significant proportion of patients and may indicate that schizophrenia is a disorder of early neurodevelopment causing impaired cerebral lateralization.

Intrathoracic blood volume accurately reflects circulatory volume status in critically ill patients with mechanical ventilation.

Positive pressure ventilation in patients with acute respiratory failure (ARF) may render the interpretation of central venous pressure (CVP) or pulmonary wedge pressure (PCWP) difficult as indicators of circulating volume. The preload component of cardiac (CI) and stroke index (SI) is also influenced by the increased intrathoracic pressures of positive pressure ventilation. Moreover CI and SI do not indicate volume status exclusively but also contractility and afterload. We investigated whether intrathoracic blood volume (ITBV) more accurately reflects blood volume status and the resulting oxygen transport (DO2). CVP, PCWP, cardiac (CI) and stroke index (SI) were measured, oxygen transport index (DO2I) and oxygen consumption index (VO2I) were calculated in 21 ARF-patients. Ventilatory patterns were adjusted as necessary. CI, SI and intrathoracic blood volume index (ITBVI) were derived from thermal dye dilution curves which were detected with a 5 F fiberoptic thermistor femoral artery catheter and fed into a thermal-dye-computer. All data were collected in intervals of 6 h. There were 224 data sets obtained. Linear regression analysis was performed between absolute values as well as between the 6 changes (prefix delta).(ABSTRACT TRUNCATED AT 250 WORDS)

New monitors of intravascular volume: a comparison of arterial pressure waveform analysis and the intrathoracic blood volume.

OBJECTIVE: Two new monitoring techniques, the analysis of arterial pressure waveform during mechanical ventilation and the determination of intrathoracic blood volume, were evaluated for preload assessment in a model of graded hemorrhage. DESIGN: 8 anesthetized dogs bled of 10, 20, and 30% of their blood volume, then retransfused and volume loaded with plasma expander. Central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output, parameters of the arterial pressure waveform analysis [systolic pressure variation (SPV) and delta down (dDOWN)], and intrathoracic blood volume (ITBV) were measured at baseline and after each stage of hemorrhage and volume expansion. RESULTS: The stroke volume index decreased significantly from 1.3 +/- 0.4 ml/kg at baseline to 0.7 +/- 0.2 ml/kg at 30% hemorrhage and then increased after retransfusion and volume loading. The changes in the filling pressures during the various stages of hemorrhage were in the range of 1-2 mmHg. CVP decreased from 5.5 +/- 0.9 to 3.1 +/- 1.7 mmHg and PCWP from 8.0 +/- 0.8 to 5.1 +/- 1.2 mmHg at 30% hemorrhage. Both filling pressures responded significantly to retransfusion; PCWP also changed in response to a volume load. SPV and dDOWN (expressed as percent of the systolic blood pressure during a short apnea) increased significantly from 6.7 +/- 1.7 and 5.6 +/- 3.2%, respectively, at baseline, to 9.7 +/- 2.6 and 8.1 +/- 2.9% after 10% blood loss and to 13.1 +/- 3.9 and 11.1 +/- 3.8% after 30% hemorrhage. ITBV decreased significantly from 29.7 +/- 4.5 to 26.8 +/- 5.3 ml/kg after 10% blood loss and to 23.1 +/- 3.0 ml/kg after 30% hemorrhage. ITBV, SPV, and dDOWN responded significantly to retransfusion and volume load. Significant correlations were found between the degree of volume change and dDOWN (r = 0.93), SPV (r = 0.96), ITBV (r = 0.95), CVP (r = 0.82), and PCWP (r = 0.90). CONCLUSIONS: The parameters of arterial pressure waveform analysis (SPV and dDOWN) and ITBV were sensitive estimates of cardiac preload during the early stages of hemorrhage. Measurement of SPV and dDOWN, being both sensitive and relatively noninvasive, has advantages over other methods of preload assessment but is limited to patients on controlled mechanical ventilation. ITBV, which supplies quantitative information about cardiac preload, is more invasive but can also be used in patients who are breathing spontaneously or who are on partial ventilatory support.

Monitoring of right ventricular function using a conventional slow response thermistor catheter.

OBJECTIVE: To investigate whether determination of right ventricular end-diastolic volume (RVEDV) and right ventricular ejection fraction (RVEF) can be performed with reasonable accuracy and reproducibility using a conventional slow response thermistor pulmonary artery catheter (CPAC) applying an adaptive algorithm. DESIGN: To study RVEDV and RVEF simultaneously with pulmonary artery catheters equipped with slow and fast response thermistors (FRPAC) under a broad range of cardiac output. SETTING: Laboratory of Institute of Experimental Surgery, Technical University. ANIMALS: 11 anaesthetised piglets. INTERVENTIONS: Hypovolemia (V-) was induced by withdrawal of blood up to 50 ml/kg, hypervolemia (V+) was produced by retransfusing blood and adding up to 30 mg/kg hydroxyethyl starch. In 5 animals in phases V- and V+ beta-adrenergic stimulation was achieved with dobutamine. Finally pulmonary artery hypertension was induced by infusion of small air bubbles. MEASUREMENTS AND RESULTS: Cardiac output (CO), RVEDV and RVEF were determined simultaneously with FRPAC and CPAC placed in the same pulmonary artery branch. Measurements were repeated 8 times sequentially in steady state normovolemia. A total of 130 measurements could be analysed. The coefficient of variation was 6.7 +/- 4.2% for CO(FRPAC) and 4.6 +/- 1.7% for CO(CPAC); for RVEF it was 9.7 +/- 6.2% (FRPAC) and 9.9 +/- 3.9% (CPAC); for RVEDV it was 11.6 +/- 4.8% (FRPAC) and 8.54 +/- 3.2 (CPAC). Mean difference (bias) was 0.06 +/- 0.39 l/min for CO measured with both methods, 19 +/- 35 ml for RVEDV and -3.3 +/- 6.5% for RVEF. CO(CPAC) displayed a strong correlation to CO(FRPAC) (R = 0.97, p = 0.001) as well as RVEF (R for RVEF(CPAC) versus RVEF(FRPAC) = 0.90, p = 0.001). R for RVEDV(CPAC) versus RVEDV(FRPAC) was 0.67, p = 0.001. We conclude that this animal study demonstrates good agreement between RVEF and RVEDV obtained with catheters equipped with a fast response thermistor or with a conventional slow response thermistor allowing accurate monitoring of right ventricular function with a conventional pulmonary artery catheter.

Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution.

OBJECTIVE: Transpulmonary double-indicator dilution is a useful monitoring technique for measurement of intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). In this study, we compared a simpler approach using single arterial thermodilution derived measurements of ITBV and EVLW with the double-indicator dilution technique. DESIGN: Prospective observational clinical study. SETTING: Surgical intensive care units of two university hospitals. PATIENTS AND METHODS: Global end-diastolic volume (GEDV) derived from single thermodilution was used for calculation of ITBV. Structural regression analysis of the first two thermo-dye dilution measurements in a derivation population of 57 critically ill patients (38 male, 19 female, 18-79 years, 56 +/- 15 years) revealed ITBV = (1.25 x GEDV)-28.4 (ml). This equation was then applied to all first measurements in a validation population of 209 critically ill patients (139 male, 70 female, 10-88 years, mean 53 +/- 19 years), and single-thermodilution ITBV (ITBV(ST)) and EVLW (EVLW(ST)) was calculated and compared to thermo-dye dilution derived values (ITBV(TD), EVLW(TD)). For inter-individual comparison, absolute values for ITBV and EVLW were normalised as indexed by body surface area (ITBVI) and body weight (EVLWI), respectively. MEASUREMENTS AND RESULTS: Linear regression analysis yielded a correlation of ITBVI(ST) = (1.05 x ITBVI(TD))-58.0 (ml/m2), r = 0.97, P < 0.0001. Bias between ITBVI(TD) and ITBVI(ST) was 7.6 (ml/m2) with a standard deviation of 57.4 (ml/m2). Single-thermodilution EVLWI (EVLWI(ST)) was calculated using ITBVI(ST) and revealed the correlation EVLWI(ST) = (0.83 x EVLWI(TD)) + 1.6 (ml/kg), r = 0.96, P < 0.0001. Bias between EVLWI(TD) and EVLWI(ST) was -0.2 (ml/kg) with a standard deviation of 1.4 (ml/kg). In detail, EVLWI(ST) systematically overestimated EVLWI(TD) at low-normal values for EVLWI and underestimated EVLWI at higher values (above 12 ml/kg). CONCLUSION: Determinations of ITBV and EVLW by single thermodilution agreed closely with the corresponding values from the double-indicator technique. Since transpulmonary single thermodilution is simple to apply, less invasive and cheaper, all these features make it a promising technique for the bedside. Nevertheless, further validation studies are needed in the future.

Influence of the beta-1 selective blocker, metoprolol, on the development of pulmonary edema in tocolytic therapy.

Research on one group of nine anesthetized dogs pretreated with alpha-naphthyl-thiourea showed that doses of the beta-sympathicomimetic fenoterol such as those normally administered in clinical tocolysis (2 micrograms/kg per minute) lead to significant fluid displacement to the extravascular space of the lung in the sense of a preclinical interstitial edema. In a second group (N = 9) with the same pretreatment the addition of the beta-1 selective blocker, metoprolol (1.5 micrograms/kg per minute) served to antagonize the hemodynamic changes and possibly the increase of pulmonary capillary permeability induced by the beta-mimetic. Fluid displacement into the interstitium of the lung was prevented by metoprolol. These observations corroborate the hypothesis that pulmonary edema occurring during tocolytic therapy is largely a result of the use of beta-mimetics. In addition to its cardioprotective effect, the administration of the beta-1 selective blocker, metoprolol, may reduce the risk of the development of pulmonary edema in beta-sympathicomimetic therapy for premature labor.

Assessment of perioperative glycerol metabolism by stable isotope tracer technique.

The aim of this study was to investigate metabolic changes during and after abdominal hysterectomy with specific regard to glycerol metabolism. Seven otherwise healthy patients with benign uterine myoma were enrolled in this study. Glycerol turnover and hepatic glucose production were measured before and after the operation by using stable-isotope technique ([1,1,2,3,3-2H5]-glycerol, [6,6-2H2]-glucose). Metabolic substrates (glycerol, nonesterified fatty acids, beta-hydroxybutyrate, glucose, lactate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra- and postoperatively. Hysterectomy was associated with an increase of postoperative glycerol turnover from 3.56 +/- 1.28 to 6.46 +/- 2.44 mumol.kg-1.min-1 (P < 0.05). This increment was inversely related to the age of the patients (r = 0.872, P < 0.05). Glycerol concentration tended to increase perioperatively. These changes, however, were not of statistical significance. Hepatic glucose production and glucose plasma levels increased postoperatively from 9.75 +/- 1.61 to 12.79 +/- 1.45 mumol.kg-1.min-1 (P < 0.05) and 4.6 +/- 0.9 to 6.2 +/- 0.9 mmol/L (P < 0.05), respectively. Cortisol and catecholamine levels rose during and after surgery, while insulin and glucagon remained unchanged. The enhanced rate of lipolysis after hysterectomy was not detectable from plasma glycerol levels alone. The results of this study showed that using stable isotope technique allowed a more differentiated look at metabolic pathways than static plasma substrate concentrations, especially under perioperative conditions.

Central venous pressure, pulmonary artery occlusion pressure, intrathoracic blood volume, and right ventricular end-diastolic volume as indicators of cardiac preload.

PURPOSE: Central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP) and right ventricular end-diastolic volume (RVEDV) are often regarded as indicators of both circulating blood volume and cardiac preload. to evaluate these relationships, the response of each variable to induced volume shifts was tested. The relationships between these variables and cardiac index (CI) and stroke volume index (SVI) was also recorded to assess the utility of each variable as an indicator of cardiac preload. The responses of the new variable intrathoracic blood volume (ITBV) to the same maneuvers was also tested. To examine the effects of changes in cardiac output alone on ITBV, the effects of infusing dobutamine were studied. MATERIALS AND METHODS: Ten anesthetized piglets were studied during conditions of normovolemia, hypovolemia, and hypervolemia. The effects of an infusion of dobutamine were examined under normovolemia and hypovolemia. Cardiac output was measured by thermo-dilution, and ITBV was measured by double-indicator dilution. RESULTS: CI was correlated to CVP with r2 = .42 (P < or = .01), to PAOP with r2 = .43 (P < or = .01), to RVEDV index with r2 = .21 (P < or = .01), and to ITBV with r2 = .78 (P < or = .01) (pooled absolute values). Bias (mean difference of the percent changes with normovolemia = 100%) +/- 1 SD; for SVI - ITBV index was 1 +/- 22%, for SVI - CVP it was -128 +/- 214%; for SVI - PAOP it was -36 +/- 46%; and for SVI - RVEDV index it was 1 +/- 29%. Dobutamine infusion increased heart rate (to about 190 x min-1 and CI by 30% in normovolemia and hypovolemia, while ITBV remained basically unchanged. CONCLUSIONS: Under the experimental conditions chosen neither CVP, PAOP, nor RVEDV reliably indicated changes in circulating blood volume, nor were they linearly and tightly correlated to the resulting changes in SVI. ITBV reflected both changes in volume status and the resulting alteration in cardiac output. The possibility that ITBV might be cardiac output-dependent was not supported. ITBV, therefore, shows potential as a clinically useful indicator of overall cardiac preload.

A clinical randomized study on the effects of invasive monitoring on burn shock resuscitation.

BACKGROUND: Ever since Charles Baxter's recommendations the standard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury. A growing number of studies on invasive monitoring in burn shock, however, have raised a debate regarding the adequacy of this regime. The purpose of this prospective, randomised study was to compare goal-directed therapy guided by invasive monitoring with standard care (Baxter formula) in patients with burn shock. PATIENTS AND METHODS: Fifty consecutive patients with burns involving more than 20% body surface area were randomly assigned to one of two treatment groups. The control group was resuscitated according to the Baxter formula (4 ml/kg BW/% BSA burn), the thermodilution (TDD) group was treated according to a volumetric preload endpoint (intrathoracic blood volume) obtained by invasive haemodynamic monitoring. RESULTS: The baseline characteristics of the two treatment groups were similar. Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group (P = 0.0001). The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters. Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups. Mortality and morbidity were independent on randomisation. CONCLUSION: Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn. Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration. Increased crystalloid infusion does not improve preload or cardiac output parameters. This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock.

Myocardial salvage prior to emergency coronary bypass surgery for PTCA-induced coronary occlusion.

The possibility of prolonged, selective coronary perfusion via angioplasty catheters was evaluated. A pump was developed featuring minimal hemolysis even at high pump pressures. Pressure requirements differed greatly between various catheter types. Catheter-induced hemolysis did not correlate with pump pressure and was mainly due to a turbulent jet effect through sideholes. In 20 of 22 closed-chest dogs, myocardial ischemia could be greatly reduced or completely prevented for over 2 hours after proximal LAD or Cx occlusion. With flow rates between 1 and 2.5 ml/min/kg body weight and using the ECG and coronary venous O2 saturation for rate adjustment, pressure within the selectively perfused vessel never reached critical values. Thus, with the appropriate equipment, prolonged coronary perfusion is feasible. In some cases of percutaneous transluminal coronary angioplasty-(PTCA) induced coronary occlusion, it may prevent ischemic myocardial damage between PTCA-induced acute coronary occlusion and subsequent surgical revascularization.