Filip Fredén

Prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis : a computerized tomography study

Background:Morbidly obese patients show impaired pulmonary function during anesthesia and paralysis, partly due to formation of atelectasis. This study analyzed the effect of general anesthesia and three different ventilatory strategies to reduce the amount of atelectasis and improve respiratory function. Methods:Thirty patients (body mass index 45 ± 4 kg/m2) scheduled for gastric bypass surgery were prospectively randomized into three groups: (1) positive end-expiratory pressure of 10 cm H2O (PEEP), (2) a recruitment maneuver with 55 cm H2O for 10 s followed by zero end-expiratory pressure, (3) a recruitment maneuver followed by PEEP. Transverse lung computerized tomography scans and blood gas analysis were recorded: awake, 5 min after induction of anesthesia and paralysis at zero end-expiratory pressure, and 5 min and 20 min after intervention. In addition, spiral computerized tomography scans were performed at two occasions in 23 of the patients. Results:After induction of anesthesia, atelectasis increased from 1 ± 0.5% to 11 ± 6% of total lung volume (P < 0.0001). End-expiratory lung volume decreased from 1,387 ± 581 ml to 697 ± 157 ml (P = 0.0014). A recruitment maneuver + PEEP reduced atelectasis to 3 ± 4% (P = 0.0002), increased end-expiratory lung volume and increased Pao2/Fio2 from 266 ± 70 mmHg to 412 ± 99 mmHg (P < 0.0001). PEEP alone did not reduce the amount of atelectasis or improve oxygenation. A recruitment maneuver + zero end-expiratory pressure had a transient positive effect on respiratory function. All values are presented as mean ± SD. Conclusions:A recruitment maneuver followed by PEEP reduced atelectasis and improved oxygenation in morbidly obese patients, whereas PEEP or a recruitment maneuver alone did not.

One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: an experimental study

BACKGROUND One-lung ventilation (OLV) increases mechanical stress in the lung and affects ventilation and perfusion (V, Q). There are no data on the effects of OLV on postoperative V/Q matching. Thus, this controlled study evaluates the influence of OLV on V/Q distribution in a pig model using a gamma camera technique [single-photon emission computed tomography (SPECT)] and relates these findings to lung histopathology after OLV. METHODS Eleven anaesthetized and ventilated pigs (V(T)=10 ml kg(-1), Fio2=0.40, PEEP=5 cm H2O) were studied. After lung separation, OLV and thoracotomy were performed in seven pigs (OLV group). During OLV and in a two-lung ventilation (TLV), control group (n=4) ventilation settings remained unchanged. SPECT with (81m)Kr (ventilation) and (99m)Tc-labelled macro-aggregated albumin (perfusion) was performed before, during, and 90 min after OLV/TLV. Finally, lung tissue samples were harvested and examined for alveolar damage. RESULTS OLV affected ventilation and haemodynamic variables, but there were no differences between the OLV group and the control group before and after OLV/TLV. SPECT revealed an increase of perfusion in the dependent lung compared with baseline (49-56%), and a corresponding reduction of perfusion (51-44%) in non-dependent lungs after OLV. No perfusion changes were observed in the control group. This resulted in increased low V/Q regions and a shift of V/Q areas to 0.3-0.5 (10(-0.5)-10(-0.3)) in dependent lungs of OLV pigs and was associated with an increased diffuse alveolar damage score. CONCLUSIONS OLV in pigs results in a substantial V/Q mismatch, hyperperfusion, and alveolar damage in the dependent lung and may thus contribute to gas exchange impairment after thoracic surgery.

Nitric Oxide Modulation of Pulmonary Blood Flow Distribution in Lobar Hypoxia

Background Nitric oxide, endogenously produced or inhaled, has been shown to play an important role in the regulation of pulmonary blood flow. The inhalation of nitric oxide reduces pulmonary arterial pressure in humans, and the blockade of endogenous nitric oxide production increases the pulmonary vascular response to hypoxia. This study was performed to investigate the hypothesis that intravenous administration of an nitric oxide synthase inhibitor and regional inhalation of nitric oxide can markedly alter the distribution of pulmonary blood flow during regional hypoxia. Methods Hypoxia (5% Oxygen2) was induced in the left lower lobe of the pig, and the blood flow to this lobe was measured with transit‐time ultrasound. Nitric oxide was administered in the gas ventilating the hypoxic lobe and the hyperoxic lung regions with and without blockade of endogenous nitric oxide production by means of Nomega ‐nitro‐L‐arginine methyl ester (L‐NAME). Results Hypoxia in the left lower lobe reduced blood flow to that lobe to 27 plus/minus 3.9% (mean plus/minus SEM) of baseline values (P < 0.01). L‐NAME caused a further reduction in lobar blood flow in all six animals to 12 plus/minus 3.5% and increased arterial oxygen tension (Pa sub O2) (P < 0.01). Without L‐NAME, the inhalation of nitric oxide (40 ppm) to the hypoxic lobe increased lobar blood flow to 66 plus/minus 5.6% of baseline (P < 0.01) and, with L‐NAME, nitric oxide delivered to the hypoxic lobe resulted in a lobar blood flow that was 88 plus/minus 9.3% of baseline (difference not significant). When nitric oxide was administered to the hyperoxic lung regions, after L‐NAME infusion, the blood flow to the hypoxic lobe decreased to 2.5 plus/minus 1.6% of baseline and PaO2 was further increased (P < 0.01). Conclusions By various combinations of nitric oxide inhalation and intravenous administration of an nitric oxide synthase inhibitor, lobar blood flow and arterial oxygenation could be markedly altered during lobar hypoxia. In particular, the combination of intravenous L‐NAME and nitric oxide inhalation to the hyperoxic regions almost abolished perfusion of the hypoxic lobe and resulted in a PaO2 that equalled the prehypoxic values. This possibility of adjusting regional blood flow and thereby of improving PaO2 may be of value in the treatment of patients undergoing one‐lung ventilation and of patients with acute respiratory failure.

Real‐time ventilation and perfusion distributions by electrical impedance tomography during one‐lung ventilation with capnothorax

Carbon dioxide insufflation into the pleural cavity, capnothorax, with one‐lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting.

Pulmonary vasoconstriction during regional nitric oxide inhalation: evidence of a blood-borne regulator of nitric oxide synthase activity.

BackgroundInhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. MethodsNitric oxide concentration was measured in exhaled air (NOE), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [Fio2] = 0.05), with and without INO to HL (Fio2 = 0.8), and during cross-circulation of blood from pigs with and without INO. ResultsLeft lower lobar hypoxia increased exhaled NO from the LLL (NOELLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86]vs. 162 [96] pmol · g−1 · min−1, P < 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol · g−1 · min−1 (P < 0.01), and NOELLL to 2.0 [0.8] ppb (P < 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NOELLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol · g−1 · min−1 (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions. ConclusionsInhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.

Matrix Metalloproteinases -8 and -9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study

Introduction Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Results Plasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.

Improved ventilation―perfusion matching with increasing abdominal pressure during CO2-pneumoperitoneum in pigs

Background: CO2‐pneumoperitoneum (PP) is performed at varying abdominal pressures. We studied in an animal preparation the effect of increasing abdominal pressures on gas exchange during PP.

No effect of metabolic acidosis on nitric oxide production in hypoxic and hyperoxic lung regions in pigs

Aim:  In the severely ill intensive care patients metabolic acidosis and hypoxia often co‐exist. We studied the effects of metabolic acidosis on nitric oxide synthase (NOS) dependent and NOS independent nitric oxide (NO) production in hypoxic and hyperoxic lung (HL) regions in a pig model.

Distant effects of nitric oxide inhalation in endotoxemic pigs

Objective:Inhalation of nitric oxide (INO) has distant effects. By a blood– borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO. Design:Prospective, randomized animal study. Setting:University hospital research laboratory. Subjects:Twenty-two pairs of domestic pigs. Interventions:Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group). Measurements and Main Results:NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca2+-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004). Conclusions:As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.

Glucocorticoid receptor expression and binding capacity in patients with burn injury

Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.