Heparin-binding protein in ventilator-induced lung injury.

BACKGROUND: Although mechanical ventilation is often lifesaving, it can also cause injury to the lungs. The lung injury is caused by not only high pressure and mechanical forces but also by inflammatory processes that are not fully understood. Heparin-binding protein (HBP), released by activated granulocytes, has been indicated as a possible mediator of increased vascular permeability in the lung injury associated with trauma and sepsis. We investigated if HBP levels were increased in the bronchoalveolar lavage fluid (BALF) or plasma in a pig model of ventilator-induced lung injury (VILI). We also investigated if HBP was present in BALF from healthy volunteers and in intubated patients in the intensive care unit (ICU). METHODS: Anaesthetized pigs were randomized to receive ventilation with either tidal volumes of 8 ml/kg (controls, n = 6) or 20 ml/kg (VILI group, n = 6). Plasma and BALF samples were taken at 0, 1, 2, 4, and 6 h. In humans, HBP levels in BALF were sampled from 16 healthy volunteers and from 10 intubated patients being cared for in the ICU. RESULTS: Plasma levels of HBP did not differ between pigs in the control and VILI groups. The median HBP levels in BALF were higher in the VILI group after 6 h of ventilation compared to those in the controls (1144 ng/ml (IQR 359-1636 ng/ml) versus 89 ng/ml (IQR 33-191 ng/ml) ng/ml, respectively, p = 0.02). The median HBP level in BALF from healthy volunteers was 0.90 ng/ml (IQR 0.79-1.01 ng/ml) as compared to 1959 ng/ml (IQR 612-3306 ng/ml) from intubated ICU patients (p < 0.001). CONCLUSIONS: In a model of VILI in pigs, levels of HBP in BALF increased over time compared to controls, while plasma levels did not differ between the two groups. HBP in BALF was high in intubated ICU patients in spite of the seemingly non-harmful ventilation, suggesting that inflammation from other causes might increase HBP levels.

Percutaneously inserted long-term central venous catheters in pigs of different sizes.

Pigs are used for long-term biomedical experiments requiring repeated injections, infusions and collections of blood samples. Thus, it is necessary for vascular catheters to be indwelling to avoid undue stress to the animals and the use of restraints. We propose a refined model of percutaneous insertion of long-term central venous catheters to minimize the surgical trauma and postoperative complications associated with catheter insertion. Different sizes of needles (18 Ga versus 21 Ga) for initial puncture of the veins were compared. In conventional pigs weighing less than 30 kg, catheter insertion may be facilitated by using a microintroducer set with a 21 Ga needle. In pigs weighing 50 kg, a standard 18 Ga needle may be preferable.

Physiological responses to touch massage in healthy volunteers.

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 80 min, 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 1 h after intervention or control, respectively. RESULTS: After 5 min 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.

Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.

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.

Do lung recruitment maneuvers decrease gastric mucosal perfusion?

OBJECTIVE: To evaluate effects of lung recruitment maneuvers on gastric mucosal perfusion, systemic circulation, and lung mechanics in patients with acute lung injury. DESIGN: Prospective observational clinical study. SETTING. General intensive care unit of university hospital. PATIENTS AND PARTICIPANTS: Fourteen patients with acute lung injury (ten in the main study group and four in a validation group). INTERVENTIONS. Three 2-min-long recruitment maneuvers (RM) with transient increases in mean airway pressure to 35 cmH(2)O (RM1 and RM2) and 44 cmH(2)O (RM3). MEASUREMENTS AND RESULTS: Measurements of systemic hemodynamics, gastric mucosal perfusion (laser Doppler flowmetry), and lung mechanics were performed immediately before, at the end of, and 3 min after each RM. Cardiac index decreased during all RMs while mean arterial pressure decreased only during RM3. Gastric mucosal perfusion was not significantly changed during any of the RMs. When comparing values obtained before the first RM with values after the third RM there was a significant decrease in cardiac index ( P=0.043) and a non-significant ( P=0.051) decrease in gastric mucosal perfusion. There were no significant changes in systemic oxygenation or lung mechanics after three RMs, even though four patients showed marked transient increases in systemic oxygenation during RMs. CONCLUSIONS: In this study of ten patients there were no significant changes in gastric mucosal perfusion during lung recruitment maneuvers. There was, however, a trend towards gradual decreases in gastric mucosal perfusion.

Does dopexamine influence regional vascular tone and oxygenation during intestinal hypotension?

BACKGROUND: Local effects of dopexamine on intestinal vascular tone and oxygenation were investigated during intestinal hypotension. To this end, we employed an experimental model, in which the superior mesenteric arterial pressure (PSMA) was controlled by an adjustable perivascular clamp. This approach enabled us to keep the intestinal perfusion pressure (IPP) constant in the face of any systemic circulatory alterations. METHODS: In 11 barbiturate-anesthetized pigs, we instrumented the superior mesenteric circulation for assessments of vascular resistance (RMES), IPP, jejunal mucosal perfusion (Laser Doppler) and intestinal tissue oxygenation (microoximetry). Measurements were carried out before and during dopexamine infusions (0.5 and 1.0 micro g.kg-1.min-1) at a freely variable PSMA (i.e. the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. RESULTS: At a constant PSMA of 50 mmHg, dopexamine had no significant intestinal vascular effects. However, at a constant PSMA of 30 mmHg, both doses of dopexamine were associated with decreases in RMES. Effects of dopexamine on intestinal oxygen delivery and extraction were minimal during these procedures, while a minor decrease in intestinal tissue oxygen tension was observed during dopexamine administration at the lowest IPP level. CONCLUSION: At very low intestinal perfusion pressures (approximately 30 mmHg) dopexamine produces intestinal vasodilation in excess of what is produced by intrinsic autoregulation. This suggests that there is a vasodilatory reserve in the intestine under such conditions and that a pharmacological vasodilator like dopexamine may improve intestinal circulation during regional severe hypotension.

Splanchnic vasoconstriction by angiotensin II is arterial pressure dependent.

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.

Effects of positive end-expiratory pressure on intestinal circulation during graded mesenteric artery occlusion.

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.

Cutaneous sympathetic vasoconstrictor reflexes for the evaluation of interscalene brachial plexus block.

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.

Continuous interscalene brachial plexus block for postoperative analgesia following shoulder surgery.

BACKGROUND: Severe postoperative pain is a well-known problem following shoulder surgery. This study evaluates the clinical efficacy of continuous interscalene brachial plexus block, patient-controlled analgesia, and morphine (i.v. and i.m.) for postoperative analgesia in this setting. METHODS: Thirty patients, scheduled for acromioplasty during general anesthesia, were randomly allocated to one of three different postoperative pain management groups. Group MO received morphine (5 mg i.m. and 2 mg i.v.) when visual analogue pain score (VAS) > 3, group PL received a continuous interscalene brachial plexus block with bupivacaine (1.25 mg kg-1 + 0.25 mg kg-1 h-1) and group PCA received patient-controlled analgesia with morphine (bolus 1 mg). Postoperative pain relief was assessed (24 h) by VAS, circulatory and respiratory stress parameters (heart rate, systemic arterial pressure and respiratory rate) and stress metabolites (glucose, lactate, glycerol by abdominal subcutaneous microdialysis). RESULTS: Pain relief in the PL group was effective (VAS < 3) and significantly more potent than in groups MO and PCA, except at 16 and 20 h. Lactate was significantly increased in the PL group, glucose was significantly increased in all groups, while glycerol showed a variable pattern. There were no significant stress metabolite differences among groups. VAS showed no statistical correlation with microdialysate, respiratory or circulatory data. CONCLUSION: Successful continuous interscalene brachial plexus block provides very good pain relief following shoulder surgery and is superior to the other methods studied. However, we were unable to demonstrate a correlation between VAS pain scores and stress indicators in metabolic, circulatory and respiratory parameters.