Interventions on arterial pressure and perfusion flow rate during cardiopulmonary bypass : effects on global fluid shifts, cerebral metabolic and structural markers in a porcine model

Global and regional organ perfusion during cardiopulmonary bypass (CPB) depends on hemodynamic parameters as mean arterial pressure (MAP) and perfusion flow rate. These parameters may also exert influence on the load of micro-emboli delivered to the central nervous system (Sungurtekin et al., 1999), to the operating conditions (Cartwright & Mangano, 1998) and to the degree of extravascular fluid accumulation during CPB (Paper III). The present thesis focus on some specific consequences of different MAP and perfusion flow rate values during CPB. Two particular endpoints have been addressed: A. Net fluid balance and fluid extravasation rate during CPB (Paper I - III) B. Cerebral biochemical changes associated with energy metabolism and ultrastructural integrity (Paper IV – V) Paper I compares a group of animals with lowered MAP (LP-group, n=7) by use of nitroprusside and a historical control group (C-group, n=7)) with respect to fluid shifts. Paper II compares groups with elevated MAP by norepinephrine (HP-group, n=8)) and lowered MAP by phentolamine (LP-group, n=8)), also with respect to fluid shifts. Paper III determines fluid shifts in groups with two different CPB perfusion flow rates (LFgroup, n=8 and HF-group, n=8). Paper IV assesses cerebral biochemical markers in groups with elevated MAP by norepinephrine (HP-group, n=6) and lowered MAP by nitroprusside (LP-group, n=6). Paper V assesses the same cerebral markers as well as mitochondrial ultrastructure by electron microscopy in animals with elevated MAP by norepinephrine (HP-group, n=8) and lowered MAP by phentolamine (LP-group, n=8). Methods: Young pigs aged 10-12 weeks were given general anesthesia and underwent 60 minutes of normothermic CPB (38°C) followed by 90 minutes of hypothermic CPB (28°C). Acetated Ringer’s solution was given with 5 ml/kg/h i.v. and as CPB prime. Extra acetated Ringer’s solution was added to the CPB venous reservoir whenever necessary, to maintain a constant level. In paper I, II, IV and V infusions of vasoactive agents were given during the whole CPB period. MAP was kept between 60 – 80 mmHg in the animals with elevated arterial pressure and at 40 – 45 mmHg in the animals with reduced arterial pressure. The two groups of animals in paper III had CPB perfusion flow rate set to 80 ml/kg/min and 110 ml/kg/min, respectively. Colloid osmotic pressure in plasma and interstitial fluid (wick method) was measured in addition to acid base parameters and blood chemistry. Plasma volume was determined by the carbon-monoxide method and subsequent changes were calculated based on new values of hematocrit and the measured amount of bleeding. Fluid extravasation rate was calculated as net fluid balance minus the change in plasma volume over a defined period of time. Intracranial pressure was monitored. Cerebral glucose, lactate, pyruvate and glycerol were measured by microdialysis. After each experiment, total tissue water content was determined in relevant organs. In paper V, cerebral tissue from cortex and thalamus in two animals from each group, were examined by electron microscopy. Results: Paper I: Net fluid balance was higher in the LP-group as compared with the C-group after 30 min of CPB. Fluid extravasation rate tended to be higher in the LP-group. The animals of the LPgroup did have higher tissue water content in the myocardium, skin and gastrointestinal tract as compared with the control group. Paper II: Plasma volume was higher in the LP-group as compared with the HP-group after 60 minutes of CPB. Net fluid balance and fluid extravasation rate did not differ between the two study groups. Left myocardial tissue water content was slightly higher in the LP-group compared with the HP-group. Paper III: Plasma volume was higher in the HF-group compared with the LF-group after 60 minutes of CPB. During the initial phase of CPB, fluid extravasation rate was significantly higher in the HF-group. The average net fluid balance during CPB was higher and the average fluid extravasation rate tended strongly to be higher in the HF-group as compared with the LF group (P=0.07). Total tissue water content of the kidneys were higher in the HF-group and tended to be higher in most other organs as compared with the LF-group. Paper IV: Intracranial pressure increased in both groups during CPB. Intracerebral glucose decreased while lactate-pyruvate ratio and cerebral glycerol increased significantly during CPB in the LP-group as compared with pre-bypass values. The values remained stable and within normal range in the HP-group. Paper V: Cerebral lactate was higher in LP-group as compared with HP-group during normothermic CPB. Compared to baseline, cerebral glucose decreased and cerebral lactate, lactate-pyruvate ratio and glycerol increased in the LP-group during normothermic CPB. The values remained unchanged in the HP-group. Electron microscopy of cortical and thalamic tissue, showed a higher frequency of altered mitochondria in the LP-group as compared with the HP-group. Conclusion: Paper I-II suggest that different levels of MAP by use of nitroprusside, phentolamine or norepinephrine have essentially no influence on fluid extravasation rate. An impact on net fluid balance was found in paper I. Paper III demonstrate that elevation of CPB flow rate to 110 ml/kg/min, may lead to higher positive net fluid balance and probably higher fluid extravasation rate as compared with a CPB flow rate of 80 ml/kg/min. Plasma volume was affected by the use of these vasoactive agents and was significantly higher in the study groups receiving phentolamine as compared with norepinephrine. Indeed, plasma volume was also affected by CPB flow rate, resulting in higher values in the experimental group with higher CPB flow rate. In paper IV and V we found that a reduction of MAP to about 40 mmHg during CPB by nitroprusside or phentolamine was associated with changes in cerebral markers of metabolism and membrane integrity compatible with cerebral ischemia and membrane degradation. Electron microscopic examination of cortical and thalamic tissue demonstrated a high frequency of mitochondrial alterations in two animals with reduced MAP by phentolamine in paper V

Norske tenåringsmødre - få, men fattige

Artiklene i Samfunnsspeilet er tilgjengelige fra SSBs nettsider: http://www.ssb.no/ssp/Det blir stadig færre tenåringsmødrer i Noreg, samstundes er dei økonomiske levekåra til desse mødrene klårt dårlegare enn for mødrer som får barn seinare i livet. I 2001 hadde tenåringsmødrer meir enn tre gonger så stort sannsyn for å ha låginntekt som andre mødrer, og dei får langt oftare stønader som sosialhjelp og bustøtte. Sjølv etter fleire år klarer ikkje dei kvinnene som fekk barn som tenåringar å henta inn att forspranget i inntekt som dei andre mødrene har. Tvert i mot ser skilnadene ut til å auka. Å bli tenåringsmor kan vera inngangen på ein dårleg sirkel som kan resultera i dårlege økonomiske levekår seinare i livet

Acute elevation of intra-abdominal pressure contributes to extravascular shift of fluid and proteins in an experimental porcine model

Background: Intra-abdominal hypertension and abdominal compartment syndrome contribute significantly to increased morbidity and mortality in critically ill patients. This study describes pathophysiologic effects of the acutely elevated intra-abdominal pressure on microvascular fluid exchange and microcirculation. The resulting changes could contribute to development of organ dysfunction or failure. Methods: 16 pigs were randomly allocated to a control-group (C-group) or an interventional group (P-group). After 60 min of stabilization, intra-abdominal pressure of the P-group animals was elevated to 15 mmHg by Helium insufflation and after 120 min to a level of 30 mmHg for two more hours. The C-group animals were observed without insufflation of gas. Laboratory and hemodynamic parameters, plasma volume, plasma colloid osmotic pressure, total tissue water content, tissue perfusion, markers of inflammation and cerebral energy metabolism were measured and net fluid balance and fluid extravasation rates calculated. Analysis of variance for repeated measurements with post-tests were used to evaluate the results with respect to differences within or between the groups. Results: In the C-group hematocrit, net fluid balance, plasma volume and the fluid extravasation rate remained essentially unchanged throughout the study as opposed to the increase in hematocrit (P < 0.001), fluid extravasation rate (P < 0.05) and decrease in plasma volume (P < 0.001) of the P-group. Hemodynamic parameters remained stable or were slightly elevated in the C-group while the P-group demonstrated an increase in femoral venous pressure (P < 0.001), right atrial pressure (P < 0.001), pulmonary capillary wedge pressure (P < 0.01) and mean pulmonary arterial pressure (P < 0.001). The protein mass decreased in both study groups but was significantly lower in the P-group as compared with the C-group, after 240 min of intervention. The increased intra-abdominal pressure was associated with elevated intracranial pressure and reduced tissue perfusion of the pancreas and the gastric- and intestinal mucosa. Conclusion: Elevation of intra-abdominal pressure has an immediate impact on microvascular fluid extravasation leading to plasma volume contraction, reduced cardiac output and deranged perfusion of abdominal organs

Aetiology, antimicrobial therapy and outcome of patients with community acquired severe sepsis: a prospective study in a Norwegian university hospital

Background: Severe sepsis is recognized as an inflammatory response causing organ dysfunction in patients with infection. Antimicrobial therapy is the mainstay of treatment. There is an ongoing demand for local surveillance of sepsis aetiology and monitoring of empirical treatment recommendations. The present study was established to describe the characteristics, quality of handling and outcome of patients with severe sepsis admitted to a Norwegian university hospital. Methods: A one year prospective, observational study of adult community acquired case-defined severe sepsis was undertaken. Demographics, focus of infection, microbiological findings, timing and adequacy of empirical antimicrobial agents were recorded. Clinical diagnostic practice was evaluated. Differences between categorical groups were analysed with Pearson’s chi-squared test. Predictors of in-hospital mortality were identified in a multivariate stepwise backward logistic regression model. Results: In total 220 patients were identified, yielding an estimated annual incidence of 0.5/1000 inhabitants. The focus of infection was established at admission in 69%. Respiratory tract infection was present in 52%, while genitourinary, soft tissue and abdominal infections each were found in 12-14%. Microbiological aetiology was identified in 61%; most prevalent were Streptococcus pneumoniae, Escherichia coli and Staphylococcus aureus. Independent predictors of in-hospital mortality were malignancy, cardiovascular disease, endocarditis, abdominal infections, undefined microbiological aetiology, delay in administration of empirical antimicrobial agents ≥ 6 hours and use of inadequate antimicrobial agents. In patients ≥ 75 years, antimicrobial therapy was less in compliance with current recommendations and more delayed. Conclusions: Community acquired severe sepsis is common. Initial clinical aetiology is often revised. Compliance with recommendations for empirical antimicrobial treatment is lowest in elderly patients. Our results emphasizes that quick identification of correct source of infection, proper sampling for microbiological analyses, and fast administration of adequate antimicrobial agents are crucial points in the management of severe sepsis