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A large degree of variability for batched analysis of serially collected microdialysis samples measured with the CMA 600 analyser has been described. This study was designed to identify sources of variability related to sample handling. Standard concentrations of four solutes were placed in microdialysis vials and then stored and analysed at intervals. Results were analysed for variability related to vial and cap type, duration and temperature of storage, centrifugation and re-analysis. The main results were that centrifugation of samples reduced variability. When a batch of 24 samples was analysed, the use of crimp caps reduced evaporation. Samples in glass vials with crimp caps could be stored in a refrigerator for up to 14 days without large variability in concentration compared to plastic vials which demonstrated variability already when stored for more than 1 day. We conclude that variability in microdialysis results can occur in relation to storage and analysis routines if routines are not optimised concerning evaporation. Centrifugation before analyses, glass vials with crimp caps even during frozen storage, and attention to minimal times for samples to be uncapped during analysis all contribute to minimise variability in the handling and analysis of microdialysis samples.

Background: To investigate whether surface microdialysis (μD) sampling in probes covered by a plastic film, as compared to noncovered and to intraparenchymatous probes, would increase the technique's sensitivity for pathophysiologic events occurring in a liver ischemia-reperfusion model. Placement of μD probes in the parenchyma of an organ, as is conventionally done, may cause adverse effects, e.g., bleeding, possibly influencing outcome.

Methods: A transient ischemia-reperfusion model of the liver was used in six anesthetized normoventilated pigs. μD probes were placed in the parenchyma and on the liver surface. Surface probes were either left uncovered or were covered by plastic film.

Results: Lactate and glucose levels were significantly higher in plastic film covered probes than in uncovered surface probes throughout the ischemic period. Glycerol levels were significantly higher in plastic film covered probes than in uncovered surface probes at 30 and 45 min into ischemia.

Conclusions: Covering the μD probe increases the sensibility of the μD–technique in monitoring an ischemic insult and reperfusion in the liver. These findings confirm that the principle of surface μD works, possibly replacing need of intraparenchymatous placement of μD probes. Surface μD seemingly allows, noninvasively from an organ's surface, via the extracellular compartment, assessment of intracellular metabolic events. The finding that covered surface μD probes allows detection of local metabolic changes earlier than do intraparenchymatous probes, merit further investigation focusing on μD probe design.

To improve the reliability of microdialysis measurements of tissue concentrations of metabolic substances, this study was designed to test both the performance and the internal validity of the microdialysis methods in the hands of our research group. The stability of the CMA 600 analyser was tested with a known glucose solution in 72 standard microvials and in 48 plastic vials. To evaluate if variation in sampling time makes any difference in sample concentration (recovery), sampling times of 10, 20 and 30 min were compared in vitro with a constant flow rate of 1 microl/min. For testing of sampling times at different flow rates, an in vitro study was performed in which a constant sample volume of 10 microl was obtained. With the no net flux method, the actual concentration of glucose and urea in subcutaneous tissue was measured. The CMA 600 glucose analysis function was accurate and stable with a coefficient of variability (CV) of 0.2-0.55%. There was no difference in recovery for the CMA 60 catheter for glucose when sampling times were varied. Higher flow rates resulted in decreased recovery. Subcutaneous tissue concentrations of glucose and urea were 4.4 mmol/l and 4.1 mmol/l, respectively. To conclude, this work describes an internal validation of our use of the microdialysis system by calibration of vials and catheters. Internal validation is necessary in order to be certain of adequate sampling times, flow rates and sampling volumes. With this in mind, the microdialysis technique is useful and appropriate for in vivo studies on tissue metabolism.

Microdialysis (MD) can be used to study metabolism of the beating heart. We investigated whether microdialysis results obtained from epicardial (surface) sampling reflect acute changes in the same way as myocardial sampling from within the substance of the ventricular wall. In anaesthetized open-thorax pigs a coronary snare was placed. One microdialysis probe was placed with the sampling membrane intramyocardially (myocardial), and a second probe was placed with the sampling membrane epicardially (surface), both in the area which was made ischaemic. Ten minutes collection intervals were used for microdialysis samples. Samples from 19 pigs were analysed for lactate, glucose, pyruvate and glycerol during equilibration, baseline, ischaemia and reperfusion periods. For both probes (surface and myocardial), a total of 475 paired simultaneous samples were analysed. Results from analyses showed no differences in relative changes for glucose, lactate and glycerol during baseline, ischaemia and reperfusion. Surface microdialysis sampling is a new application of the microdialysis technique that shows promise and should be further studied.

Introduction. We recently have shown that samples from MD probes placed on the surface of the heart reflect metabolic events in the myocardium. This new interesting observation challenges us to consider whether surface application of MD applies to other parenchymatous organs and their surfaces.

Material and methods.  In thirteen anesthetized pigs transient liver ischemia was achieved by occlusion of arterial and venous inflow to the liver. Two probes on liver surface, and two in parenchyma were perfused with a flow rate of 1 µL/min (n=13). An identical set up was used for probes with a flow rate of 2 µL/min (n=9). Samples were collected for every 15 minute period during 60 minutes of baseline, 45 minutes of ischemia and 60 minutes of reperfusion. Lactate, glucose, pyruvate and glycerol were analysed in MD samples. We focused on relative changes in the present paper.

Results. There was a strong agreement in relative lactate and glucose levels between probes placed on liver surface and parenchyma. No significant differences in relative changes of lactate and glucose levels were seen between samples from surface probes and probes in liver parenchyma during equilibration, baseline, ischemia or reperfusion with a flow rate of 1 µL/min.

Conclusion. MD sampling applied on the liver surface is a new application area for the MD technique, and may be used to monitor liver metabolism both during physiological and pathophysiological conditions.

We recently have shown that samples from microdialysis (MD) probes placed on the surface of the heart reflect metabolic events in the myocardium. This new interesting observation challenges us to consider whether surface application of MD applies to other parenchymatous organs and their surfaces. In 13 anesthetized pigs, transient liver ischaemia was achieved by occlusion of arterial and venous inflow to the liver. Two probes on liver surface and two in parenchyma were perfused with a flow rate of 1 mu l per min (n = 13). An identical set-up was used for probes with a flow rate of 2 mu l per min (n = 9). Samples were collected for every 15-min period during 60 min of baseline, 45 min of ischaemia and 60 min of reperfusion. Lactate, glucose, pyruvate and glycerol were analysed in MD samples. We focused on relative changes in the present study. There was a strong agreement in relative lactate and glucose levels between probes placed on liver surface and those on parenchyma. No significant differences in relative changes in lactate and glucose levels were seen between samples from surface probes and probes in liver parenchyma during equilibration, baseline, ischaemia or reperfusion with a flow rate of 1 mu l per min. MD sampling applied on the liver surface is a new application area for the MD technique and may be used to monitor liver metabolism during both physiological and pathophysiological conditions.

Background: Ischemic injury to the pancreas occurs in various clinical conditions. A method for online monitoring of pathophysiological events in pancreatic parenchyma is missing. Aims: To assess the timing of microdialysis (MD) technique response on temporary changes in pancreatic perfusion, and to evaluate the relationship between MD data and systemic markers of anaerobic metabolism and inflammation. Methods: In anaesthetized normoventilated pigs, MD probes were placed in right (control) and left (ischemic) pancreatic lobes, respectively. Following the clamping of the vessels, ischemia was verified by tissue oxygen tension (PtiO2) measurements. Results: PtiO2 decreased within 20 min after the clamping of the vessels, already returning to baseline levels at the first sampling point after the removal of the clamp. MD lactate levels increased, whereas pyruvate and glucose levels decreased at 20 min after the induction of ischemia. These trends continued until the end of ischemia and returned to baseline following reperfusion. Serum lactate, amylase and tumor necrosis factor-alpha levels decreased throughout the protocol time. Conclusion: MD data were in concordance with changes in PtiO2, which is indicative of local anaerobic metabolism. MD allowed the detection of pathophysiological processes within the ischemic pancreas at a stage when no elevations of systemic markers of ischemia or inflammation were observed.

BACKGROUND: Our hypothesis was that splanchnic vasoconstriction by exogenous angiotensin II (Ang II) is significantly potentiated by local mechanisms increasing vasomotor tone and that splanchnic tissue oxygenation during administration of Ang II is perfusion pressure dependent. The aim was to study local splanchnic circulatory effects and tissue oxygenation during intravenous infusion of Ang II at different levels of regional arterial driving pressure in a whole-body large animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h-1) in anaesthetised instrumented pigs (n=8). Mean superior mesenteric arterial pressure (PSMA) was adjusted by a local variable perivascular occluder. Perivascular ultrasound and laser-Doppler flowmetry were used for measurements of mesenteric venous blood flow and superficial intestinal blood flow, respectively. Intestinal oxygenation was evaluated by oxygen tissue tension (PtiO2) and lactate fluxes. RESULTS: Ang II produced prominent and dose-dependent increases in mesenteric vascular resistance (RSMA) when the intestine was exposed to systemic arterial pressure, but Ang II increased RSMA only minimally when PSMA was artificially kept constant at a lower level (50 mmHg) by the occluder. Although Ang II decreased PtiO2 at a PSMA of 50 mmHg, splanchnic lactate production was not observed. CONCLUSION: We demonstrate that splanchnic vasoconstriction by exogenous Ang II is dependent on arterial driving pressure, suggesting significant potentiation through autoregulatory increases in vasomotor tone. Intestinal hypoxaemia does not seem to occur during short-term infusion of Ang II in doses that significantly increases systemic arterial pressure.

BACKGROUND: Post-craniotomy intracranial air can be present in patients scheduled for air ambulance transport to their home hospital. We aimed to assess risk for in-flight intracranial pressure (ICP) increases related to observed intracranial air volumes, hypothetical sea level pre-transport ICP, and different potential flight levels and cabin pressures. METHODS: A cohort of consecutive subdural hematoma evacuation patients from one University Medical Centre was assessed with post-operative intracranial air volume measurements by computed tomography. Intracranial pressure changes related to estimated intracranial air volume effects of changing atmospheric pressure (simulating flight and cabin pressure changes up to 8000 ft) were simulated using an established model for intracranial pressure and volume relations. RESULTS: Approximately one third of the cohort had post-operative intracranial air. Of these, approximately one third had intracranial air volumes less than 11 ml. The simulation estimated that the expected changes in intracranial pressure during 'flight' would not result in intracranial hypertension. For intracranial air volumes above 11 ml, the simulation suggested that it was possible that intracranial hypertension could develop 'inflight' related to cabin pressure drop. Depending on the pre-flight intracranial pressure and air volume, this could occur quite early during the assent phase in the flight profile. DISCUSSION: These findings support the idea that there should be radiographic verification of the presence or absence of intracranial air after craniotomy for patients planned for long distance air transport. CONCLUSIONS: Very small amounts of air are clinically inconsequential. Otherwise, air transport with maintained ground-level cabin pressure should be a priority for these patients.

Background: There are three different types of ambulance systems, all of which can manage the same secondary intensive care patient transport mission: road ambulance, rotor-wing ambulance, and fixed-wing ambulance. We hypothesized that costs for specific transport distances would differ between systems. We aimed to analyze distances and observed times for ambulance intensive care secondary transport missions together with system costs to assess this. Methods: We prospectively collected data for consecutive urgent intensive care transports into the regional tertiary care hospital in the northern region of Sweden. Distances and transport times were gathered, and a cost model was generated based on these together with fixed and operating costs from the three different ambulance systems. Distance-cost and time-cost estimations were then generated for each transport system. Results: Road ambulance cost relatively less for shorter distances (within 250 kilometers/155 miles) but were relatively time ineffective. The rotor-wing systems were most expensive regardless of distance; but were most time-effective up to 400-500 km (248-310 miles). Fixed-wing systems were more cost-effective for longer distance (300 km/186 miles), and time effective for transports over 500 km (310 miles). Conclusions: In summary, based on an economic model developed from observed regional ICU patient transports, and cost estimations, different ambulance system cost-distances could be compared. Distance-cost and time results show that helicopters can be effective up to moderate ICU transport distances (400-500), though are expensive to operate. For longer ICU patient transports, fixed-wing transport systems are both cost and time effective compared to helicopter-based systems.

This study was performed to establish a platform for further studies on effects of ventilatory treatment modalities on the intestines during mechanical ventilation of acute lung injury (ALI). We tested the hypotheses that oleic acid (OA) infusion causes changes in intestinal circulation, oxygenation and metabolism, and that OA is distributed to tissues outside the lung. This was performed as an experimental, prospective and controlled study in an university animal research laboratory. Thirteen juvenile anaesthetized pigs were used in the main study, where seven were given an intravenous infusion of 0.1 ml kg(-1) OA and six served as control (surgery only). In a separate study, four animals were given an intravenous infusion of 0.1 ml kg(-1) (3)H-labelled OA. We measured systemic and mesenteric (portal venous blood flow, jejunal mucosal perfusion) haemodynamic parameters, mesenteric oxygenation (jejunal tissue oxygen tension) and systemic cytokines (tumour necrosis factor-alpha and interleukin-6). We calculated mesenteric lactate flux and mesenteric oxygen delivery, uptake and extraction ratio. In the animals given 3H-OA, we measured 3H-OA in different tissues (lungs, heart, liver, kidney, stomach, jejunum, colon and arterial blood). We found that OA given intravenously is distributed in small amounts to the intestines. This intestinal exposure to OA does not cause intestinal injury when evaluating mesenteric blood flow, metabolism or oxygenation. OA infusion induced a moderate increase in mean pulmonary arterial pressure and a decrease in PaO2/Fraction inspired O2 (P/F) ratio, giving evidence of severe lung injury. Consequently, the OA lung injury model is suitable for studies on intestinal effects of ventilatory treatment modalities during mechanical ventilation of ALI.

OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.

To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.

This self-controlled experimental study was designed to test the hypothesis that dopexamine, a synthetic catecholamine that activates dopaminergic (DA-1) and beta2-adrenergic receptors, improves oxygenation in the jejunal mucosa during intestinal hypotension. In six normoventilated barbiturate-anesthetized pigs, controlled reductions in superior mesenteric arterial pressure (PSMA) was obtained by an adjustable clamp around the artery. Dopexamine infusions (0.5 and 1.0 microg.kg(-1).min(-1)) were administered at a freely variable PSMA (i.e., with the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. We continuously measured superior mesenteric venous blood flow (QMES; transit-time ultrasonic flowmetry), jejunal mucosal perfusion (laser Doppler flowmetry), and tissue oxygen tension (PO2TISSUE; microoximetry). Jejunal luminal microdialysate of lactate, pyruvate, and glucose were measured every 5 min. Measurements of mucosal PCO2 (air tonometry), together with blood sampling and end-tidal PCO2 measurements, enabled calculations of pHi and PCO2 gap. Dopexamine reduced mesenteric vascular resistance and increased QMES at a PSMA of 50 mmHg and 30 mmHg. At a PSMA of 30 mmHg, dopexamine increased mesenteric oxygen delivery but did not influence mesenteric oxygen uptake or extraction. In this situation, dopexamine had no beneficial effect on jejunal mucosal blood flow. On the contrary, dopexamine increased mesenteric net lactate production and PCO2 gap, whereas PO2TISSUE and pHi decreased. Jejunal luminal microdialysate data demonstrated an increased lactate concentration and a pattern of decreased glucose concentration and increased luminal lactate-pyruvate ratio. These negative metabolic effects of dopexamine should be taken into account in situations of low perfusion pressures.

OBJECTIVE: To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS: Twelve barbiturate-anaesthetized female pigs. METHODS: Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS: At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS: Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.

BACKGROUND: Little has been reported about intensive care of children in Sweden. The aims of this study are to (I) assess the number of admissions, types of diagnoses and length-of-stay (LOS) for all Swedish children admitted to intensive care during the years 1998-2001, and compare paediatric intensive care units (PICUs) with other intensive care units (adult ICUs) (II) assess immediate (ICU) and cumulative 5-year mortality and (III) determine the actual consumption of paediatric intensive care for the defined age group in Sweden. METHODS: Children between 6 months and 16 years of age admitted to intensive care in Sweden were included in a national multicentre, ambidirectional cohort study. In PICUs, data were also collected for infants aged 1-6 months. Survival data were retrieved from the National Files of Registration, 5 years after admission. RESULTS: Eight-thousand sixty-three admissions for a total of 6661 patients were identified, corresponding to an admission rate of 1.59/1000 children per year. Median LOS was 1 day. ICU mortality was 2.1% and cumulative 5-year mortality rate was 5.6%. Forty-four per cent of all admissions were to a PICU. CONCLUSIONS: This study has shown that Sweden has a low immediate ICU mortality, similar in adult ICU and PICU. Patients discharged alive from an ICU had a 20-fold increased mortality risk, compared with a control cohort for the 5-year period. Less than half of the paediatric patients admitted for intensive care in Sweden were cared for in a PICU. Studies are needed to evaluate whether a centralization of paediatric intensive care in Sweden would be beneficial to the paediatric population.

BACKGROUND: Severe sepsis and septic shock are associated with high mortality rates. Data on sepsis outcome from Scandinavian countries are sparse. The aim of this study was to examine the length of stay (LOS) in the ICU, ICU mortality and costs of care for adult patients with primary sepsis in a university hospital in northern Sweden.

METHODS: We performed a retrospective data analysis of records of 92 patients admitted over a 3-year period, under the diagnosis of sepsis or urosepsis. Demographic data, admission category, APACHE II score, aetiology and severity of sepsis, ICU LOS, mortality and TISS were analyzed.

RESULTS: Eighty-one adult patients were identified by standard definitions as suffering from sepsis. The median ICU length of stay was 4.2 days, 6 days for survivors and 2.1 days for non-survivors. Thirteen out of 20 deaths occurred within the first 3 days after admission. Overall ICU mortality rate was 24.7% while the ICU mortality for patients with septic shock was 57.7%. The mean costs of care for patients with sepsis were 3139 Euros day(-1) and the cost of care per patient surviving sepsis was 38,494 Euros.

CONCLUSION: The incidence of primary sepsis in our ICU was low. Previous reports on high mortality in association with severe sepsis and septic shock are valid also at our hospital. The ICU-LOS was shorter than previously reported, while our costs of care were in the same range as stated by others. This retrospective analysis is valid for interpretation of the applicability of currently available sepsis therapies.

Objective: To determine if levels of the adipocyte-derived hormones leptin and adiponectin (adipokines) predict sepsis development and if intra-individual changes in circulating levels from baseline to the acute phase affect outcome.

Method: A nested case-referent study within the framework of the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC). Patients aged 18 years or more with documented sepsis within 24 hours after admission to the intensive care unit (ICU) were included if they had participated in a health survey and donated blood samples prior to the sepsis event, and if possible also had stored plasma from the acute phase. Two matched referents free of known sepsis were selected for each case. Baseline and acute phase plasma leptin and adiponectin levels were determined. The associations between adipokines and sepsis and its severity and outcome were determined.

Results: We identified 57 men and 97 women with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in the health survey, and 83% of them had also samples from the acute septic phase. Hyperleptinemia associated with a future sepsis event (OR 1.77, 95% CI 1.04-3.00, P=0.03), with stronger associations with severe sepsis and septic shock than with sepsis. High leptin levels were also associated with hospital death in the fully adjusted model. Leptin remained associated with sepsis in men (P=0.02), but not in women (P=0.36), after stratification and adjustment for BMI. In the acute phase, leptin increased more in men than in women (P=0.001), and high leptin levels were associated with increased risk for in-hospital death in women (OR 4.18, 95%CI 1.17-15.00, P=0.03), while being protective in men (OR 0.05, 95% CI 0.01-0.48, P=0.01). Adiponectin did not associate with sepsis or outcome.

Conclusions: Hyperleptinemia independently predicted the development of sepsis, and an unfavourable outcome in men. Adiponectin was not associated with sepsis development.

Background: Mannose-binding lectin (MBL) mediates the innate immune response either through direct opsonisation of microorganisms or through activation of the complement system. There are conflicting data whether MBL deficiency leads to increased susceptibility to infections or not. The aim of this study was to determine if low levels of mannose-binding lectin (MBL) predict sepsis development, sepsis severity and outcome from severe sepsis or septic shock.

Method: Patients aged 18 years or more with documented sepsis within 24 h after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Plasma levels MBL were determined in stored samples from health surveys (baseline) and from ICU admission (acute phase). The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined with 1300 ng/mL as cut-off for low levels.

Results: We identified 148 patients (61.5% women) with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 122 also had samples from the acute septic phase. Both high MBL levels in the acute phase (odds ratio [95% confidence interval]) (2.84 [1.20-6.26]), and an increase in MBL levels from baseline to the acute phase (3.76 [1.21-11.72]) were associated with increased risk for in-hospital death in women, but not in men (0.47 [0.11-2.06]). Baseline MBL levels did not predict future sepsis, sepsis severity or in-hospital mortality.

Conclusions: An increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.

Background: Controversy exists regarding the influence of gender on sepsis events and out­come. Epidemiological data from other countries may not always apply to local circum­stances.  The aim of this study was to identify gender differences in patient characteristics, treatment and outcome related to the occurrence of sepsis at admission to the ICU.

Methods: A prospective observational cohort study on patients admitted to the ICU over a three-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate and aspects of treatment were collected and then analysed with respect to gender differences.

Results: There were no gender related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mor­tality for women than for men. This discrepancy was mainly associated with the coagulation sub score. CRP-levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women whereas infection from skin or skin structures were more common in men.

Conclusion: In this cohort, gender was not associated with increased mortality during a two year follow up period.  SOFA score at ICU-admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub score. Together with differences in CRP-levels this may suggest differences in inflammatory response patterns between genders.

Objective: To determine if levels of mannose-binding lectin (MBL) predict sepsis development and if intra-individual changes in circulating levels from baseline to the acute septic phase associate with in-hospital mortality.

Method: A nested case-referent study within the framework of the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC). Patients aged 18 years or more with documented sepsis within 24 hours after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Baseline and acute phase plasma MBL levels were determined. The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined.

Results: We identified 57 men and 95 women with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 127 also had samples from the acute septic phase. High baseline levels predicted future sepsis (OR 1.81, 95% CI 1.01-3.26), but were not associated with severity of sepsis or in-hospital fatality. Both high MBL levels in the acute phase (OR 4.94, 95% CI 1.44-16.89), and an increase from base line to the acute phase (OR 3.67, 95% CI 1.19-11.28) were associated with increased risk for in-hospital death in women, but not in men (OR 0.71, 95% CI 0.18-2.88). Low levels at baseline were not associated with future sepsis. Neither low levels at baseline, nor in the acute phase were associated with sepsis severity or in-hospital mortality.

Conclusions: High pre-sepsis levels predicted a future sepsis event, and an increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.

Background: Sepsis is a life-threatening condition and obesity is related to the clinical outcome. The underlying reasons are incompletely understood, but the adipocyte derived hormones leptin and adiponectin may be involved.

Methods: Patients aged 18 years or more with documented first time sepsis events were included in a nested case-referent study if they had participated in previous health surveys. Two matched referents free of known sepsis were identified. Circulating levels of leptin and adiponectin were determined in stored plasma, and their impact on a future sepsis event and its outcome was evaluated.

Results: We identified 152 patients (62% women) with a sepsis event and a previous participation in a health survey. Eighty-three % had also blood samples from the acute event. Hyperleptinemia at health survey associated with a future sepsis event (OR 1.77, 95% CI 1.04-3.00) and with hospital death. After adjustment for BMI leptin remained associated with sepsis in men, but not in women. High levels in the acute phase associated with increased risk for in hospital death in women (OR 4.18, 95% CI 1.17-15.00), while being protective in men (OR 0.05, 95% CI 0.01-0.48). Furthermore, leptin increased more from baseline to the acute phase in men than in women. Adiponectin did not predict sepsis and did not relate to outcome.

Conclusions: Hyperleptinemia independently predicted the development of sepsis and an unfavourable outcome in men, and inertia in the acute response related to worse outcome.

OBJECTIVE: The aim of this study was to examine the hypothesis that patients with non-traumatic subarachnoid hemorrhage (SAH) have statistically significant subnormal creatinine levels and that the creatinine levels are associated with severity of disease.

MATERIALS AND METHODS: This was a retrospective observational study over 2 years (2005-2006) in which the SAH patients were divided into patients with severe symptoms and patients with mild/moderate symptoms, and were compared to patients with; traumatic brain injury, trauma without brain injury and patients undergoing elective knee surgery. Blood creatinine levels (day 1-3, and day 7) were recorded.

RESULTS: Compared to a normal distribution, SAH patients had statistically significant subnormal creatinine levels day one through seven. SAH patients with severe symptoms had statistically significant subnormal creatinine levels already on day one, in contrast to patients with mild/moderate symptoms. Women with severe symptoms had statistically significant subnormal creatinine levels throughout the study period in contrast to men with severe symptoms who had a normal distribution of creatinine at admission. Women with mild/moderate symptoms had a normal distribution of creatinine only at admission in contrast to men who had a normal distribution of creatinine throughout the study period. Male patients with traumatic brain injury, all trauma patients without brain injury and all patients undergoing elective knee surgery had a normal distribution of creatinine on all studied days.

CONCLUSIONS: SAH is associated with subnormal serum creatinine levels. This finding is more pronounced in patients with severe symptoms and in women.

Objective: This study was aimed to evaluate the patients perspectives, before and one month after surgery in patients treated with open surgery for renal cell carcinoma (RCC). Can effective perioperative analgesia be part of a multimodal approach to minimize morbidity and improve postoperative management [1].

Material and Methods: A total of 135 patients with RCC in all stages 2012-2015, were randomized to receive either spinal analgesia with clonidine, or epidural analgesia in addition to the general anesthesia: The patients were stratified according to surgical technique. Inclusion criteria: ASA score I-III, age >18 years, no chronic pain medication or cognitive disorders. The patients survey used was based on the EORTC QLQ-C30. Wilcoxon Signed Rank test and Mann-Whitney-U tests were used for statistical evaluation.

Results: A majority of the patients (117 of 135, 86%) responded to the survey. Patients groups treated with partial nephrectomy or radical nephrectomy, had significantly reduced physical and social functioning while emotional functioning improved postoperatively compared with preoperatively. In both surgical groups the patients reported significant negative financial difficulties postoperatively. Similar results was achieved for patients treated with either spinal or epidural anesthesia. The epidural group of patients experienced more negative social functioning but had an improved global health. When comparing the surgical procedures there was no significant difference in the quality of life parameters. However when comparing the analgesic groups, spinal anesthesia had significantly better physical and social functioning after surgery while the patients in the epidural group reported better global health.

Conclusion: Patients randomized to be treated with spinal analgesia with clonidine, had better physical and social functioning postoperatively than patients randomized to be treated with epidural analgesia.

OBJECTIVE: To evaluate the net effects of the concomitant use of positive end-expiratory pressure (PEEP) and dopexamine on intestinal tissue perfusion and oxygenation during predefined artificial reductions in intestinal perfusion pressure (IPP). DESIGN: Prospective, self-controlled, experimental study. SETTING: University hospital research laboratory. SUBJECTS: Seven female pigs. MEASUREMENTS: In barbiturate-anesthetized pigs, we measured mesenteric blood flow (QMES) [by transit-time ultrasonic flowmetry], jejunal mucosal perfusion (by laser Doppler flowmetry), and tissue PO(2) (by microoximetry). Based on blood sampling, we calculated the intestinal net lactate production and oxygenation. INTERVENTIONS: These measurements and calculations were performed at three predefined and controlled IPP levels, which were obtained by an adjustable clamp around the superior mesenteric artery. At each IPP level, measurements were performed prior to and during PEEP (10 cm H(2)O), both with and without simultaneous dopexamine infusions (at 0.5 and 1.0 microg/kg/min). RESULTS: Within the IPP range of 77 to 33 mm Hg, intestinal perfusion and oxygenation were maintained irrespective of whether PEEP and/or dopexamine were applied or not. At IPP < 33 mm Hg, QMES and intestinal oxygenation deteriorated, resulting in regional net lactate production. At this IPP range, tissue oxygen perfusion was entirely pressure-dependent, and even small reductions in IPP led to prominent increases in intestinal net lactate production. Dopexamine did not modify this pattern. CONCLUSIONS: We describe maintained intestinal tissue oxygen perfusion within a wide perfusion pressure range. Within this perfusion pressure range, PEEP did not induce any adverse regional circulatory effects. Below the perfusion pressure range for effective autoregulation, intestinal tissue oxygen perfusion deteriorated, and regional ischemia occurred. In this situation, dopexamine was unable to counteract IPP-dependent decreases in intestinal tissue oxygen perfusion. The regional ischemic threshold can be defined either as an IPP of < 33 mm Hg or as an intestinal tissue PO(2) of < 45 mm Hg.

BACKGROUND: Reduced gut perfusion is associated with multiple organ failure. Positive end-expiratory pressure (PEEP) reduces cardiac output (CO) and portal blood flow, and might be detrimental in a situation of already compromised intestinal circulation. The aim of this study was to investigate regional circulatory and metabolic effects of PEEP during graded regional hypoperfusion. METHODS: In 12 barbiturate-anesthetized pigs, we measured systemic and regional blood flows (superior mesenteric arterial, QSMA and portal venous, QPORT), jejunal mucosal perfusion (LDF), tissue oxygenation (PO2TISSUE) and metabolic parameters at PEEP (0, 4, 8 and 12 cm H2O) in a randomized order. Measurements were performed at unrestricted intestinal perfusion pressures (IPP) and at IPP levels of 50 and 30 mmHg. RESULTS: During unrestricted IPP, PEEP decreased MAP, CO, QSMA and QPORT, while systemic, and preportal (RPORT) vascular resistances and jejunal mucosal perfusion were not significantly changed. Preportal tissue oxygen delivery and PO2TISSUE decreased, while preportal tissue oxygen uptake was unaltered. During restricted IPP, PEEP produced the same pattern of hemodynamic alterations as when IPP was not restricted. QPORT and QSMA were lowered by the reductions in IPP, and QPORT was further reduced during PEEP. At an IPP of 30 mmHg, this reduction in QPORT decreased preportal tissue oxygen uptake. Consequently, intestinal ischemia, as indicated by increased net lactate production, occurred. Simultaneously, jejunal mucosal perfusion and PO2TISSUE declined. CONCLUSION: At IPP levels below 50 mmHg, even moderate levels of PEEP impaired local blood flow enough to cause intestinal ischemia. Our data underscore the importance of considering regional circulatory adaptations during PEEP ventilation.

Background: Although signs of sympathetic blockade following interscalene brachial plexus block include Horner’s syndrome, increased skin temperature and vasodilatation, the degree of sympathetic blockade is not easily determined. The aim of this study was, therefore, to use activation of cutaneous finger pad vasoconstrictor reflexes for description and quantification of the degree of sympathetic blockade following unilateral interscalene brachial plexus block.

Methods: Eight patients scheduled for acromioplasty under general anesthesia were studied. An interscalene plexus catheter was inserted preoperatively on the side to be operated upon and used postoperatively for administration of bupivacaine, given as a bolus (1.25 mg kg−1) followed by a continuous infusion (0.25 mg kg−1 h−1). Skin blood flow (SBF) in the pad of the index finger was assessed by the laser Doppler technique, and regional skin vascular resistance (RVR) was calculated. The inspiratory gasp test (apnea at end‐inspiration) or a local heat provocation were used as provocations of the cutaneous microcirculation.

Results: Interscalene brachial plexus block increased SBF and decreased RVR at rest, and produced satisfactory sensory and motor block. The inspiratory gasp test decreased SBF and increased RVR in the unblocked arm, while the opposite, increased SBF and decreased RVR, were observed during local heat provocation. In the blocked arm, these gasp‐induced cutaneous vasoconstrictor and heat‐induced vasodilator responses were attenuated.

Conclusions: Interscalene brachial plexus block reduces regional sympathetic nervous activity, illustrated by increases in skin blood flow, skin temperature and attenuated vasoconstrictor responses to an inspiratory gasp. The inspiratory gasp vasoconstrictive response is a powerful and sensitive indicator for monitoring the sympathetic blockade following interscalene brachial plexus block.

Objectives: To report and evaluate a complex touch massage intervention according to the British Medical Research Council framework. This study aimed to evaluate the effects of touch massage on levels of anxiety and physiological stress in patients scheduled for elective aortic surgery.

Background: The use of touch massage has increased during the past decade but no systematic studies have been implemented to investigate the effectiveness of such treatment. It is important to conduct multidisciplinary investigations into the effects of complex interventions such as touch massage. For this, the British Medical Research Council has provided a useful framework to guide the development, piloting, evaluation and reporting of complex intervention studies.

Method: A pilot study with a randomized controlled design including 20 patients (10 + 10) scheduled for elective aortic surgery. Selected outcome parameters included; self-reported anxiety, measured by the State-Trait Anxiety Inventory Form Y instrument, and physiological stress, measured by heart rate variability, blood pressure, respiratory frequency, oxygen saturation and concentrations of cortisol, insulin and glucose in serum.

Results: There were significant differences in self-reported anxiety levels before and after touch massage (p = 0·007), this was not observed in the control group (p = 0·833). There was a significant difference in self-reported anxiety levels between the touch massage group and the control group after touch massage and rest (p = 0·001). There were no significant differences in physiological stress-related outcome parameters between patients who received touch massage and controls.

Conclusion: In our study, touch massage decreased anxiety levels in patients scheduled for elective aortic surgery, and the British Medical Research Council framework was a useful guideline for the development, evaluation and reporting of a touch massage intervention.

Relevance to clinical practice: Touch massage can reduce patients' anxiety levels and is thus an important nursing intervention in intensive and post-operative care.

OBJECTIVES: To evaluate effects of touch massage (TM) on stress responses in healthy volunteers.

METHODS: A crossover design including twenty-two (mean age=28.2) healthy volunteers (11 male and 11 female) cardiac autonomic tone was measured by heart rate (HR) and heart rate variability (HRV). Stress hormone levels (cortisol) were followed in saliva. We also measured blood glucose and serum insulin. Extracellular (ECV) levels of glucose, lactate, pyruvate and glycerol were followed using the microdialysis technique (MD). TM was performed on hands and feet for 80min, during control, participants rested in the same setting. Data were collected before, during, and after TM and at rest. Saliva cortisol, serum glucose, and serum insulin were collected before, immediately following, and 1h after intervention or control, respectively.

RESULTS: After 5min TM, HR decreased significantly, indicating a reduced stress response. Total HRV and all HRV components decreased during intervention. Saliva cortisol and insulin levels decreased significantly after intervention, while serum glucose levels remained stable. A similar, though less prominent, pattern was seen during the control situation. Only minor changes were observed in ECV levels of glucose (a decrease) and lactate (an increase). No significant alterations were observed in glycerol or pyruvate levels throughout the study. There were no significant differences between groups in ECV concentrations of analyzed substances.

CONCLUSIONS: In healthy volunteers, TM decreased sympathetic nervous activity, leading to decreased overall autonomic activity where parasympathetic nervous activity also decreased, thereby maintaining the autonomic balance.

Background: Predicting major post-operative complications is an important task for which simple and reliable methods are lacking. A simple scoring system based on intraoperative heart rate, blood pressure and blood loss was recently developed to fill this gap. This system, the Surgical Apgar Score, shows promising results both in terms of validity and in terms of usefulness. The goal of this study was to study both these components in a Scandinavian setting.

Methods: Pre-operative patient characteristics and intraoperative variables were recorded for 224 patients undergoing general and vascular surgery between 26 October and 17 December 2009. Major complications were evaluated during a 30-day follow-up. The relationship between Surgical Apgar Score and major complication was analysed using chi(2) -tests and the relative risk between different scoring patient groups was analysed.

Results: The study showed a strong correlation between the Surgical Apgar Score and major complication (P<0.001). 61.5% of the lowest-scoring patients sustained a major complication compared with only 6.4% in the highest-scoring group. This is equivalent to a relative risk of 7.14 (95% CI: 2.88-17.5, P<0.001).

Conclusions: The Surgical Apgar Score is valid in a Scandinavian setting. We also note that there were no practical issues in collecting the score. Together with patient pre-operative risk, the score has great potential to guide clinicians when making post-operative decisions and give immediate feedback about the surgical procedure. The next step should be to educate surgical staff about the score.

BACKGROUND: Preoperative venous return (VR) optimization and adequate blood volume is essential in management of morbidly obese patients (MO) in order to avoid perioperative circulatory instability. In this study, all subjects underwent a preoperative 3-week preparation by rapid-weight-loss-diet (RWL) as part of their treatment program for bariatric surgery.

METHODS: This is a prospective, observational study of 34 morbidly obese patients consecutively scheduled for bariatric surgery at Sunderby County Hospital, Lulea, Sweden. Preoperative transthoracic echocardiography (TTE) was performed in the awake state before and after intravascular volume challenge (VC) of 6 ml colloids/kg ideal body weight (IBW). Effects of standardized VC were evaluated by TTE. Dynamic and non-dynamic echocardiographic indices for VC were studied. Volume responsiveness and level of VR before and after VC were assessed by TTE. An increase of stroke volume >/=13 % was considered as a volume responder.

RESULTS: Twenty-nine out of 34 patients were volume responders. After VC, a majority of patients (23/34) were euvolemic, and only 2/34 were hypovolemic. Post-VC hypervolemia was observed in 9/34 of patients.

CONCLUSIONS: The IBW-based volume challenge regime was found to be suitable for preoperative rehydration of RWL-prepared MO. Most of the patients were volume responders. Preoperative state of VR was not associated with volume responsiveness. IBW estimates and appropriate monitoring avoids potential hyperhydration in MO. For VC assessment, conventional Doppler indices were found to be more suitable compared to tissue Doppler, giving sufficient information on pressure-volume correlation of the left ventricle in morbidly obese.

BACKGROUND: In morbidly obese patients (MO), adequate levels of venous return (VR) and left ventricular filling pressures (LVFP) are crucial in order to augment perioperative safety. Rapid weight loss (RWL) preparation with very low calorie diet is commonly used aiming to facilitate bariatric surgery. However, the impact of RWL on VR and LVFP is poorly studied.

METHODS: In this prospective, controlled, single-center study, we hypothesized that RWL-prepared MO prior to bariatric surgery can be hypovolemic (i.e., low VR) and compared MO to lean controls with conventional overnight fasting. Twenty-eight morbidly obese patients were scheduled consecutively for bariatric surgery and 19 lean individuals (control group, CG) for elective general surgery. Preoperative assessment of VR, LVFP, and biventricular heart function was performed by a transthoracic echocardiography (TTE) protocol to all patients in the awake state. Assessment of VR and LVFP was made by inferior vena cava maximal diameter (IVCmax) and inferior vena cava collapsibility index- (IVCCI) derived right atrial pressure estimations.

RESULTS: A majority of MO (71.4 %) were hypovolemic vs. 15.8 % of lean controls (p < 0.001, odds ratio = 13.3). IVCmax was shorter in MO than in CG (p < 0.001). IVCCI was higher in MO (62.1 +/- 23 %) vs. controls (42.6 +/- 20.8; p < 0.001). Even left atrium anterior-posterior diameter was shorter in MO compared to CG.

CONCLUSIONS: Preoperative RWL may induce hypovolemia in morbidly obese patients. Hypovolemia in MO was more common vs. lean controls. TTE is a rapid and feasible tool for assessment of preload even in morbid obesity.

Background and objective: The interest in bariatric surgery is growing. Morbidly obese patients have an increased risk of hypoxia and decreased blood pressure during rapid sequence induction (RSI). Alternate RSI methods that provide cardiovascular and respiratory stability are required. With this in mind, we evaluated a method for volatile RSI in morbidly obese patients.

Design: Observational study.

Methods: Thirty-four patients with mean BMI 42.4 kg m(-2) undergoing bariatric surgery (morbidly obese group) and 22 patients with mean BMI 25.6 kg m(-2) as a control group were included in the study. Anaesthesia was induced with sevoflurane, propofol, suxamethonium and alfentanil, designed to avoid respiratory and haemodynamic adverse events and to minimise depressing effect on the brain respiratory centre under ongoing RSI. Peripheral oxygen saturation (SpO(2)) and mean arterial blood pressure were registered before and after endotracheal intubation. In addition, two time periods were measured during RSI: spontaneous breathing time (SBT) and apnoea time.

Results: We found no significant differences between the groups. No periods of desaturation were detected. SpO(2) was 100% before and after endotracheal intubation in all patients. Mean arterial pressure was maintained at a stable level in both groups. Mean SBT and apnoea time were 65.6 and 45.8 s in the morbidly obese group, and 70.7 and 47.7 s in the control group, respectively.

Conclusion: A combination of sevoflurane, propofol, suxamethonium and alfentanil is a suitable method for RSI which maintains cardiovascular and respiratory stability in both morbidly obese and lean patients.

Background

In bariatric surgery, non-or mini-invasive modalities for cardiovascular monitoring are addressed to meet individual variability in hydration needs. The aim of the study was to compare conventional monitoring to an individualized goal-directed therapy (IGDT) regarding the need of perioperative fluids and cardiovascular stability. 

Methods

Fifty morbidly obese patients were consecutively scheduled for laparoscopic bariatric surgery (ClinicalTrials.gov Identifier: NCT01873183). The intervention group (IG, n=30) was investigated preoperatively with transthoracic echocardiography (TTE) and rehydrated with colloid fluids if a low level of venous return was detected. During surgery, IGDT was continued with a pulse-contour device (FloTrac (TM)). In the control group (CG, n=20), conventional monitoring was conducted. The type and amount of perioperative fluids infused, vasoactive/inotropic drugs administered, and blood pressure levels were registered. 

Results

In the IG, 213 +/- 204 mL colloid fluids were administered as preoperative rehydration vs. no preoperative fluids in the CG (p<0.001). During surgery, there was no difference in the fluids administered between the groups. Mean arterial blood pressures were higher in the IG vs. the CG both after induction of anesthesia and during surgery (p=0.001 and p=0.001). 

Conclusions

In morbidly obese patients suspected of being hypovolemic, increased cardiovascular stability may be reached by preoperative rehydration. The management of rehydration should be individualized. Additional invasive monitoring does not appear to have any effect on outcomes in obesity surgery.

BACKGROUND: The key regulator of intravascular fibrinolysis, tissue-type plasminogen activator (t-PA), is released from a dynamic endothelial storage pool. The aim of the study was to investigate regional t-PA net release and uptake rates in response to infra-renal aortic cross-clamping (AXC) and declamping (DC). METHODS: Anesthetized pigs were studied during 5 min of AXC, followed by a 35-min declamping (DC) period. Arterio-venous concentration gradients of total and active t-PA, as well as respective plasma flows, were simultaneously obtained across the preportal, hepatic, coronary and pulmonary vascular beds. Plasma levels of total t-PA (ELISA with purified porcine t-PA as standard), and active t-PA (spectrophotometric functional assay) were determined. RESULTS: Prior to AXC, we found a high net release rate of total t-PA across the preportal vascular bed (1700 ng.min-1 P < 0.001), and a high hepatic net uptake (4900 ng.min-1, P < 0.001), while coronary and pulmonary t-PA net fluxes were small and variable. AXC per se did not induce significant alterations in net fluxes of t-PA. Following DC, preportal and coronary net releases of total t-PA increased (to 2900 ng.min-1 and 60 ng.min-1, respectively). Despite an increase in hepatic net uptake of total t-PA (to 6100 ng.min-1) after DC, a significant increase in hepatic venous total t-PA occurred. CONCLUSIONS: The release and uptake of t-PA is indicated to be dynamic and organ-specific. DC induces an acute profibrinolytic reaction in preportal organs. The high hepatic t-PA uptake capacity restricts preportal profibrinolytic events to affect the systemic circulation.

INTRODUCTION: Continuous positive airway pressure (CPAP) is used in air ambulances to treat patients with impaired oxygenation. Differences in mechanical principles between CPAP devices may affect their performance at different ambient air pressures as will occur in an air ambulance during flight. METHODS: Two different CPAP systems, a threshold resistor device and a flow resistor device, at settings 5 and 10 cm H₂O were examined. Static pressure, static airflow and pressure during simulated breathing were measured at ground level and at three different altitudes (2400 m (8 kft), 3000 m (10 kft) and 10700 m (35 kft)). RESULTS: When altitude increased, the performance of the two CPAP systems differed during both static and simulated breathing pressure measurements. With the threshold resistor CPAP, measured pressure levels were close to the preset CPAP level. Static pressure decreased 0.71 ± 0.35 cm H₂O, at CPAP 10 cm H₂O, comparing ground level and 35 kft. With the flow resistor CPAP, as the altitude increased CPAP produced pressure levels increased. At 35 kft, the increase was 5.13 ± 0.33 cm H₂O at CPAP 10 cm H₂O. DISCUSSION: The velocity of airflow through the flow resistor CPAP device is strongly influenced by reduced ambient air pressure leading to a higher delivered CPAP effect than the preset CPAP level. Threshold resistor CPAP devices seem to have robust performance regardless of altitude. Thus, the threshold resistor CPAP device is probably more appropriate for CPAP treatment in an air ambulance cabin, where ambient pressure will vary during patient transport.

BACKGROUND: The Boussignac CPAP has been found to effectively treat acute pulmonary oedema. However, data on airway pressure in association with the Boussignac CPAP are sparse. We therefore designed this study to evaluate the stability of the Boussignac CPAP in terms of maintaining adequate inspiratory and expiratory pressure levels. We also wanted to evaluate the perceived exertion when breathing with the Boussignac CPAP.

METHODS: Continuous recordings of airway pressure and airflow were made in 18 healthy volunteers during breathing with the Boussignac CPAP at 5, 7.5 and 10 cm H₂O for three sessions of 10 minutes at each CPAP level. Participants were blinded for the sequential order of the investigated CPAP levels. They terminated each session, at the respective CPAP level, by taking 10 forced breaths.

RESULTS: During 10 minutes normal breathing periods, when participants breathed at 20 % of their VC with a peak expiratory airflow of 14 % of FEV₁, the maximal pressure difference was 4.0 cm H₂O between inspiration and expiration at CPAP 10 cm H₂O. Changes in airway pressure were never large enough to reduce airway pressure below zero. When taking forced breaths, expiratory volume was 38-42 % of VC and peak expiratory airflow was 49-56 % of FEV ₁. As airflow increased, both the drop in inspiratory airway pressure and the increase in expiratory airway pressure were enhanced.

CONCLUSIONS: Pressure changes during breathing with CPAP are considered to be associated with increased work of breathing. The pneumatic performance of the Boussignac CPAP is adequate during normal breathing with low airflow. However, during forced breathing resulting in increased airflow, the Boussignac CPAP is unable to maintain stable airway pressure levels, possibly resulting in increased work of breathing and respiratory fatigue. Thus, the Boussignac CPAP system might be less suitable for patients breathing at a higher frequency.

Introduction: Positive expiratory pressure (PEP) and continuous positive airway pressure (CPAP) are used to enhance breathing parameters such as functional residual capacity (FRC) in patients. Studies comparing effects of PEP and CPAP on FRC are sparse. One reason for this may be that sophisticated equipment, not suitable in the clinical setting, is required. Total lung capacity consists of inspiratory capacity (IC) and FRC and a change in IC should therefore result in a corresponding change in FRC. We aimed to investigate if PEP and CPAP induced changes in IC could be used as an indirect measure of changes in FRC and also to evaluate immediate effects of PEP and CPAP devices, with different kinds of resistors, on IC. 

Methods: 20 healthy volunteers breathed with two PEP devices, a PEP-mask (flow resistor) and a PEP-bottle (threshold resistor) and two CPAP devices, a flow resistor device and a threshold resistor device, in a randomized order. The measurement sequence consisted of 30 breaths with an IC measurement performed before and immediately after the 30^th breath, while the participants were still connected to the respective breathing device. Perceived exertion of the respective 30 breaths was measured with Borg CR10 scale.

Results: Three of the four breathing devices, the PEP-mask and the two CPAP devices, significantly decreased IC (p < 0.001). Median perceived exertion was quite low for all four breathing devices but the difference in perceived exertion within the different breathing devices was large.

Conclusion: When measured in direct continuation of PEP and CPAP breathing, changes in IC could be used as an indirect measure of changes in FRC. All investigated breathing devices except the PEP-bottle decreased IC, i.e. increased FRC.

BACKGROUND: Positive expiratory pressure (PEP) and CPAP are used to enhance breathing parameters such as functional residual capacity (FRC) in patients. Studies comparing effects of PEP and CPAP on FRC are few and variable. One reason for this may be that sophisticated equipment, not suitable in the clinical setting, is required. Because total lung capacity (TLC) consists of inspiratory capacity (IC) and FRC, a change in IC should result in a corresponding change in FRC given constant TLC. We aimed to evaluate the effects of different PEP and CPAP devices on IC as an indirect measure of induced changes in FRC from these devices in healthy subjects. METHODS: Twenty healthy subjects breathed with 2 PEP devices, a PEP mask (flow resistor) and a PEP bottle (threshold resistor), and 2 CPAP devices, a flow resistor and a threshold resistor, in a randomized order. The measurement sequence consisted of 30 breaths with an IC measurement performed before and immediately after the 30th breath while the subjects were still connected to the breathing device. Perceived exertion of the 30 breaths was measured with the Borg category ratio 10 scale. RESULTS: Three of the 4 breathing devices, the PEP mask and the 2 CPAP devices, significantly decreased IC (P <.001). Median perceived exertion was quite low for all 4 breathing devices, but the difference in perceived exertion among the different breathing devices was large. CONCLUSIONS: Provided that TLC is constant, we found that measurements of changes in IC could be used as an indirect measure of changes in FRC in healthy subjects. All investigated breathing devices except the PEP bottle decreased IC, as an indirect measure of increased FRC.

BACKGROUND: In the intensive care unit we have observed that patients have different adherence to 2 commonly used positive-expiratory-pressure (PEP) therapy devices: the PEP bottle and the PEP mask. The reason for this difference is not clear. METHODS: In a randomized prospective study, we made continuous recordings of airway pressure and airflow, with 20 healthy volunteers, with the PEP bottle and the PEP mask. The measurement sequence consisted of 3 sessions of 10 breaths with the PEP bottle and the PEP mask, in a randomized crossover design. A rest period of 15 min separated the PEP bottle and PEP mask measurements. RESULTS: With the PEP bottle the expiratory phase began with a zero-flow period of 0.39 s, during which airway pressure rose 11.9 cm H2O. With the PEP bottle the mean expiratory pressure was 11.7 cm H2O, and end-expiratory pressure was 9.5 cm H2O. With the PEP mask the initial expiratory zero-flow period was almost nonexistent (0.04 s) and without any change in airway pressure. With the PEP mask the shape of the expiratory pressure curve was different; mean expiratory pressure was 8.6 cm H2O, and end-expiratory pressure was zero. With the PEP bottle the inspiration also began with a zero-flow period of 0.43 s, during which airway pressure decreased 9.6 cm H2O from the end-expiratory airway pressure. With the PEP mask the initial inspiratory zero-flow period was only 0.01 s and there was no concomitant change in airway pressure. CONCLUSIONS: The PEP bottle and the PEP mask showed major differences in the relationship between airflow and airway pressure. These findings might explain the observed differences in patient adherence to these therapies.

The purpose of the investigation was to assess the effects of desflurane (DES) on left ventricular heart function during basal barbiturate anesthesia in a closed-pericardium, closed-chest acute swine model. The study was performed in 11 normoventilated adult pigs. Hemodynamic measurements were obtained using arterial, central venous, and pulmonary artery catheters, as well as a conductance volumetry and tip manometry catheter placed in the left ventricle. Hemodynamic measurements were recorded during basal pentobarbital anesthesia and with the addition of 1%, 2%, 4%, and 6% DES. DES dose-dependently decreased mean arterial pressure, systemic vascular resistance, left ventricular end-systolic pressure, dP/dtMAX and dP/dtMIN. At doses >1%, decreases in CO, stroke volume, ejection fraction, end-systolic elastance, preload recruitable stroke work, preload adjusted maximal power, and peak filling rate were observed. Heart rate decreased at 4% and 6% DES. Isovolumetric relaxation time increased only at 6% DES. We conclude that smaller doses of DES have a significant cardiodepressive effect in the setting of barbiturate infusion, as measured by conductance volumetry. IMPLICATIONS: Desflurane, in very small doses, depressed cardiac function during pentobarbital anesthesia with ketamine and benzodiazepine premedication in swine, as assessed by conductance volumetry and left ventricular pressure and volume relationship analysis. These results suggest that desflurane, in combination with certain anesthetics, can be cardiodepressive even in very small doses.

BACKGROUND: The aim of the present study was to analyze the perfusion pressure dependency for the splanchnic vascular effects of desflurane (DES). METHODS: We measured portal blood flow (QPORT, perivascular ultrasound) and jejunal mucosal perfusion (JMP; laser Doppler) in pentobarbital-anesthetized pigs (n=10). Experimentally, decreases in mean arterial pressure (MAP) were produced by pericardial infusions of dextran. The protocol included sets of measurements at incremental doses of DES (1, 2, 4 and 6%) prior to and during pericardial infusions. RESULTS: Although QPORT and JMP decreased significantly during pericardial infusions, DES, irrespective of dose, did not reduce QPORT until MAP had decreased below 65-70 mm Hg. In higher MAP ranges, vasodilation in pre-portal tissues was powerful enough to maintain QPORT in spite of concurrent decreases in driving arterial pressure, as produced by either DES or pericardial infusion, or by a combination of both. We found no effects of DES on JMP even at very low MAP (about 40 mm Hg during pericardial infusion), indicating that the normal physiological response of the small intestine to redistribute blood flow from deeper to more superficial layers during hypotension was unimpaired by DES. CONCLUSIONS: Our data suggest a wide dose-tolerability of DES as regards the splanchnic circulation during hypotensive states.