Surfactant Instillation Research Articles

Exogenous surfactant treatment for severe acute viral bronchiolitis: case report

OBJECTIVE: To describe the possible clinical and laboratory effects of exogenous surfactant instillation into the tracheal tube of a child with severe acute bronchiolitis undergoing mechanical ventilation. CASE REPORT: a 2-month-old girl with clinical diagnosis of acute viral bronchiolitis underwent mechanical ventilation. She required high positive inspiratory peak pressure (35 to 45 cmH(2)O) and high inspiratory fraction of oxygen (FiO(2) = 0.9), but showed no clinical response or improvement in the arterial blood gas analysis. An exogenous surfactant (Exosurf(R), Glaxo - 50 mg/kg) was used to facilitate the use of a less aggressive ventilatory strategy. RESULTS: Four hours after surfactant administration, it was possible to reduce the positive peak inspiratory pressure (PIP) from 35 to 30 cmH(2)O, and FiO(2) from 0.9 to 0.6; and to increase the positive end-expiratory pressure (PEEP) from 6 to 9 cmH(2)O. During this period the paO(2)/FiO(2) ratio increased from 120 to 266. At the end of 24 hours, FiO(2) could be reduced to 0.4. DISCUSSION: Surfactant inactivation may be a decisive factor in the unfavorable evolution of some severe cases of acute bronchiolitis. The tracheal instillation of exogenous surfactant, in these cases, allows us to adopt less aggressive ventilatory strategies, and promotes rapid clinical responses.

Application of in vivo confocal microscopy to the objective evaluation of ocular irritation induced by surfactants

An ocular irritation test using confocal laser scanning ophthalmoscopy has been developed in which corneal lesions subsequent to instillation of surfactants are specifically marked by fluorescein and assessed by digital image processing. The sum of the observed fluorescent corneal areas is taken into account as an endpoint of ocular irritation. Eight currently used nonionic, cationic and anionic surfactants were applied onto the cornea of rabbits and mice, four times per day during 3 days at various concentrations. Benzalkonium chloride, a cationic surfactant, at a concentration range of 0.01–0.5%, was tested in the same manner. The cornea was evaluated in vivo for ocular tolerance by confocal microscopy. In both rabbits and mice, the test revealed following irritation rankings: cationic>anionic>nonionic surfactants. Furthermore, in both animal models, the ocular damage increased with the concentration of benzalkonium. The test was sensitive enough to detect ocular microlesions at concentrations of surfactants as low as 0.01% for benzalkonium. These findings demonstrate the usefulness of confocal microscopy for the non-invasive, in situ evaluation of ocular tolerance.

Treatment of experimental Cryptococcus neoformans infection in newborn rabbits by airway instillation of specific antibody and surfactant.

Cryptococcosis in AIDS patients has a slow response to antifungal chemotherapy, and passive antibody treatment has thus been considered as an adjunct. Polyclonal anticryptococcal IgG dissolved in a suspension of modified natural surfactant was given intratracheally to near-term rabbits. Killing of Cryptococcus neoformans within the lungs was determined by counting the colony forming units (cfu). After 5 h a significant decrease in cfu was observed in rabbits treated with the IgG-surfactant mixture compared with control animals receiving saline. In conjunction with conventional therapy, the combined treatment of IgG-surfactant given by bronchoscopy might be used in high-risk patients to enhance killing of the yeast within the lungs.

Surfactant treatment impairs gas exchange in a canine model of acute lung injury.

The effectiveness of surfactant (SURF) treatment in acute lung injury in the adult is controversial. In this study, we tested the effectiveness of early surfactant treatment in a commonly used animal model of acute lung injury, phorbol-myristate acetate (PMA), to see if it would attenuate the progression of lung injury. We measured the effect on lung compliance and whether positive end-expiratory pressure (PEEP) (10 cm H2O) during SURF administration had a synergistic effect. Four groups of anesthetized dogs were studied: a) normals; b) PMA injury only; c) PMA injury + SURF; and d) PMA + SURF + PEEP. Lung injury was induced with 25-30 microg/kg of PMA. Responses were measured over 7 hrs. Surfactant was administered in the form of Survanta, 4 x 25 mg/kg doses via tracheal instillation 2.5 hrs after PMA. For the group receiving PEEP, 10 cm H2O PEEP was begun 1.5 hrs after PMA, 1 hr before SURF. Postmortem, the left lung was excised and inflated three times to total lung capacity (volume at 30 cm H2O) and expiratory compliance was measured with 25-100 mL volume increments. The trachea was then clamped and trapped volume was determined by water displacement. PMA-induced lung injury significantly reduced expiratory compliance and total lung capacity (p < .05 from normal). Wet/dry lung weights did not differ between groups. SURF without PEEP further decreased lung compliance as compared with PMA only. SURF administration after PMA injury causes marked reductions in lung compliance when no PEEP is coadministered. However, the loss of static expiratory lung compliance appears partly ameliorated by application of PEEP + SURF. Given that tracheal instillation of SURF is known to acutely elevate lung impedance in the first few hours after administration, coadministration of PEEP appears to be critically important in counteracting these early effects of surfactant instillation on the lung.

Cerebral Blood Flow Velocity Changes After Bovine Natural Surfactant Instillation

To determine the effects of bovine natural surfactant (beractant) instillation on cerebral hemodynamics in preterm infants with respiratory distress syndrome (RDS). Preterm infants who required surfactant for RDS were enrolled. Cerebral blood flow velocity (CBFV) waveforms from the pericallosal artery were analyzed by pulsed Doppler ultrasonography with the anterior fontanel serving as an acoustic window. CBFV was measured before and at 5, 10, 20, and 30 minutes after the first dose of a bolus instillation of surfactant in four aliquots. Simultaneously with CBFV measurements, mean blood pressure (MBP), heart rate, and ventilator settings were recorded. pH, PACO2, and PAO2 before and at 30 minutes after surfactant administration were also determined. The 30 enrolled preterm infants had a mean birth weight of 973 gm (513 to 1996 gm) and a mean gestational age of 27 weeks (23 to 33 weeks). Mean postnatal age at surfactant administration was 4.7 +/- 2.7 hours. There were no significant changes in pH and PACO2 before and at 30 minutes after surfactant (before surfactant: mean pH of 7.29 +/- 0.07 and mean PACO2 of 44.4 +/- 7.1 torr; after surfactant: mean pH of 7.31 +/- 0.07 and mean PACO2 of 42.7 +/- 8.3 torr). PAO2 increased significantly from a pre-surfactant mean of 83 torr to 130 torr at 30 minutes after surfactant (p < 0.05), with no significant changes in mean airway pressure. There were no significant changes in MBP, heart rate, mean CBFV, peak systolic flow velocity, and diastolic flow velocity before and after surfactant instillation regardless of gestational age. Individual changes in mean CBFV were related to MBP changes (p < 0.001, linear mixed models with random effects). In low birth weight infants with RDS, bovine surfactant instillation is not associated with a significant alteration in cerebral hemodynamics. However, the direct relationship between CBFV and MBP is consistent with the reported pressure-passive cerebral circulation in sick preterm infants.

Improvement in respiratory compliance after surfactant therapy evaluated by a new method.

Descriptions of the effects of intratracheally applied surfactant on respiratory system compliance (C(rs)) have been somewhat controversial because the commonly used methods for assessing pulmonary function were designed for a linear pressure/volume (P/V) relation of the respiratory system. In infants with lung disease a linear P/V relation cannot be expected. Therefore, a new method (APVNL) was employed which enabled us to calculate respiratory system compliance (C(rs)) and resistance (R(rs)) based on changes in volume (V). This method is independent of the P/V relation, and was used to assess the effects of intratracheal instillation of surfactant. Fourteen infants (gestational age, 24 to 30 weeks) with respiratory distress syndrome were treated with bovine surfactant intratracheally while the fractional inspired oxygen concentration (FiO(2)) exceeded 50%. C(rs) was evaluated for the infants using the APVNL method and the method of linear regression (LR) based on the equation of motion designed for linear P/V relationships. Two hours after surfactant treatment, the median reduction of FiO(2) was 33% (95% CI: 20-50%; P < 0.01). There was no correlation between the change in FiO(2) and the change in C(rs), using either the APVNL method or the LR method. Two hours after surfactant treatment, the median improvement in C(rs) was 0.37 mL/cmH(2)O/kg (95% CI: 0.07-1. 16 mL/cmH(2)O) at a change in V of 1 mL/kg (P < 0.02) and 0.23 mL/cmH(2)O/kg (95% CI: 0-0.57 mL/cmH(2)O) at a change in V of 2 mL/kg (P < 0.05) when the APVNL method was used. The LR method could not show a significant change in C(rs) after surfactant treatment. Further, R(rs) did not show significant changes 2 hr after surfactant administration. We conclude that the APVNL method is more appropriate for evaluating changes of C(rs) elicited by surfactant treatment than the LR method. The APVNL method demonstrated significant initial improvements in compliance as lung volumes were increased; there were no significant further decreases in C(rs) as peak inspiratory pressures and the upper limits of tidal volume were approached.

Protective effect of lung inflation in reperfusion-induced lung microvascular injury

We used the isolated-perfused rat lung model to study the influence of pulmonary ventilation and surfactant instillation on the development of postreperfusion lung microvascular injury. We hypothesized that the state of lung inflation during ischemia contributes to the development of the injury during reperfusion. Pulmonary microvascular injury was assessed by continuously monitoring the wet lung weight and measuring the vessel wall (125)I-labeled albumin ((125)I-albumin) permeability-surface area product (PS). Sprague-Dawley rats (n = 24) were divided into one control group and five experimental groups (n = 4 rats per group). Control lungs were continuously ventilated with 20% O(2) and perfused for 120 min. All lung preparations were ventilated with 20% O(2) before the ischemia period and during the reperfusion period. The various groups differed only in the ventilatory gas mixtures used during the flow cessation: group I, ventilated with 20% O(2); group II, ventilated with 100% N(2); group III, lungs remained collapsed and unventilated; group IV, same as group III but pretreated with surfactant (4 ml/kg) instilled into the airway; and group V, same as group III but saline (4 ml/kg) was instilled into the airway. Control lungs remained isogravimetric with baseline (125)I-albumin PS value of 4.9 +/- 0.3 x 10(-3) ml x min(-1) x g wet lung wt(-1). Lung wet weight in group III increased by 1.45 +/- 0.35 g and albumin PS increased to 17.7 +/- 2.3 x 10(-3), indicating development of vascular injury during the reperfusion period. Lung wet weight and albumin PS did not increase in groups I and II, indicating that ventilation by either 20% O(2) or 100% N(2) prevented vascular injury. Pretreatment of collapsed lungs with surfactant before cessation of flow also prevented the vascular injury, whereas pretreatment with saline vehicle had no effect. These results indicate that the state of lung inflation during ischemia (irrespective of gas mixture used) and supplementation of surfactant prevent reperfusion-induced lung microvascular injury.

Ultrasonic surfactant nebulization with different exciting frequencies

Intratracheal bolus instillation of natural lung surfactant is the treatment of choice in neonatal respiratory distress syndrome and an increasing part in adults’ therapy. For reasons of hemodynamics, surfactant distribution and efficiency the application mode should be improved. Nebulization seems to have some advantages but its technical realization is difficult. The aim of the present study was to investigate if ultrasonic nebulization with exciting frequencies higher than 2.8 MHz can improve the efficiency of surfactant nebulization without changing the surface-active properties of the material. Exciting frequencies of 1.7, 3.3 and 4.0 MHz were used to produce a surfactant aerosol. The phospholipid content in the liquefied aerosol and particle size distinctly dropped with higher frequencies. The surface activity was not altered in the produced aerosol and neither in the surfactant remaining in the nebulizer. Although possible, ultrasonic nebulization of surfactant suspensions is ineffective because of a striking decrease in phospholipid content.

Low-dose surfactant instillation during extracorporeal membrane oxygenation therapy in a patient with adult respiratory distress syndrome and secondary atelectasis after chest contusion

DULT RESPIRATORY DISTRESS SYNDROME (ARDS) is a serious complication in patients with chest contusion. The impaired oxygenation often cannot be improved, either by an increase of respiratory minute volume or by an increase of positive end-expiratory pressure (PEEP). Rather, barotrauma is promoted by these measures, t,2 Frequent postural change can improve the survival rate in patients with ARDS and entails only minor therapeutic interventions) ,4 Previous studies have shown that additional high-dose ambroxol therapy (3 g/24 hr) reliably reduces the incidence of ARDS or improves lung function parameters in patients with existing ARDS.5 Treatment with venovenous extracorporeal membrane oxygenation (ECMO) is an effective extension of therapy. 6 Since its introduction, the survival rate of acute, noninfectious respiratory failure has increased from 56% to 78%. 7 A further step of ARDS treatment is the administration of surfactant. Its successful use has been reported by several authors. TM Costs are extremely high, however, restricting this therapy to highly selected cases. The authors report a patient who developed severe ARDS. Even during ECMO therapy, arterial oxygenation improved only temporarily. To reduce costs and intervention time for therapeutic bronchoscopy in a critical situation, an extremely low dose of surfactant was used.

The effect of surfactant therapy for acute lung injury induced by intratracheal endotoxin instillation in rats examination of the lung

Background : Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. Methods : Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. Results : Intratracheal endotoxin instillation increased the respiration rate decreased the tidal volume and int creased the Penh in all group of rats. Intratracheal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation at both times of administration (30 minute and 5 hour after endotoxin instillation). Conclusion : Intratracheal instillation of surfactant can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated for treatment of human acute lung injury.

Influence of a Pulmonary Surfactant on the In Vitro Activity of Tobramycin against Pseudomonas aeruginosa

Delivery of therapeutic concentrations of drugs to the lung periphery is crucial in treatment of many infectious and inflammatory diseases of the lung. Conventional drug treatment for serious pulmonary infections consists of systemic administration of drug in order to achieve concentrations in the bloodstream that will reach therapeutic results. Advantages to topical drug administration to the lungs via aerosol are well known (3). However, the amount of drug that can be inhaled as aerosol is frequently small, thereby limiting the amount of drug delivered to the distal portion of the lung (1). Intratracheal instillation of surfactant, in the animal model, increased the fractional area of lung exposed and improved the uniformity of spread of radioactive label in the lung compared to the saline control (2). We examined the effect of physical perturbation with the mixture, antibiotic, and surfactant, via heat and sonication and stability over time as a function of the MIC for Pseudomonas. Tobramycin and surfactant (Exosurf suspension) were combined in cationic adjusted Mueller-Hinton broth (CAMHB) to create mixtures containing 8, 16, 32, or 64 μg of surfactant per ml, all with 4 μg of tobramycin per ml (4). One aliquot of each mixture was heated at 80°C for 30 min, one was sonicated at room temperature for 30 min, and a third was held at room temperature for 30 min without additional treatment. Serial twofold dilutions of each aliquot were prepared in CAMHB in microdilution trays (final volume, 100 μl/well) and inoculated with approximately 5 × 105 CFU of Pseudomonas aeruginosa ATCC 27853. Serial dilutions of tobramycin in CAMHB and separate serial dilutions of surfactant in CAMHB were inoculated with the same organism to serve as controls. All trays were incubated for 18 h at 35°C, and the MIC was determined visually. When tobramycin and surfactant were mixed, sonicated, and heated to 80°C for 30 min, there was no in vitro reduction in MIC for P. aeruginosa. To assess the stability of mixtures of tobramycin and surfactant, we prepared a stock mixture containing 27 mg each of tobramycin and surfactant per ml. Dilutions of this mixture were prepared immediately to give final concentrations of tobramycin ranging from 0.06 to 8 μg/ml in CAMHB. Controls, inoculation, incubation, and examination were identical to those described above. The remaining stock mixture was stored at 4°C for 3 weeks, and the MIC was determined at 1 week and again at 3 weeks. No decline in the MIC of the mixture was found when it was stored in a refrigerated environment for up to 3 weeks. van’t Veen and coworkers (5) found a reduction in bactericidal activity of tobramycin when tobramycin was mixed with surfactant which could be compensated for by increasing the tobramycin concentration. A possible explanation of the difference from our study may be the difference in the surfactants. Exosurf, a synthetic compound, does not contain protein, whereas van’t Veen et al. used a surfactant obtained from the bovine lung containing a protein component.

Effects of exogenous surfactant on acute lung injury induced by intratracheal instillation of infant formula or human breast milk in rabbits.

An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products. The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured. The acidified milk products increased A-aD(O2)(550+/-52 and 156+/-28 mmHg; mean+/-SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6+/-0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84+/-4% and 8+/-20%), and decreased compliance (0.76+/-0.09 and 1.90+/-0.11 ml/cm H2O). Surfactant improved these variables in a dose-dependent manner (A-aDO2 = 363+/-50 and 237+/-55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it. Exogenous surfactant improved physiologic, histologic, and biochemical lung injury induced by acidified milk products in a dose-dependent manner. The effectiveness of surfactant may be caused, in part, by inhibition of neutrophils' sequestration and activation. These data indicate that intratracheal instillation of surfactant may be a promising therapeutic modality in acute lung injury resulting from aspiration of acidified milk products.

Cerebral Blood Flow Velocity Changes after Bovine Natural Surfactant Instillation

OBJECTIVE: To determine the effects of bovine natural surfactant (beractant) instillation on cerebral hemodynamics in preterm infants with respiratory distress syndrome (RDS). STUDY DESIGN: Preterm infants who required surfactant for RDS were enrolled. Cerebral blood flow velocity (CBFV) waveforms from the pericallosal artery were analyzed by pulsed Doppler ultrasonography with the anterior fontanel serving as an acoustic window. CBFV was measured before and at 5, 10, 20, and 30 minutes after the first dose of a bolus instillation of surfactant in four aliquots. Simultaneously with CBFV measurements, mean blood pressure (MBP), heart rate, and ventilator settings were recorded. pH, PACO2, and PAO2 before and at 30 minutes after surfactant administration were also determined. RESULTS: The 30 enrolled preterm infants had a mean birth weight of 973 gm (513 to 1996 gm) and a mean gestational age of 27 weeks (23 to 33 weeks). Mean postnatal age at surfactant administration was 4.7 ± 2.7 hours. There were no significant changes in pH and PACO2 before and at 30 minutes after surfactant (before surfactant: mean pH of 7.29 ± 0.07 and mean PACO2 of 44.4 ± 7.1 torr; after surfactant: mean pH of 7.31 ± 0.07 and mean PACO2 of 42.7 ± 8.3 torr). PAO2 increased significantly from a pre-surfactant mean of 83 torr to 130 torr at 30 minutes after surfactant (p < 0.05), with no significant changes in mean airway pressure. There were no significant changes in MBP, heart rate, mean CBFV, peak systolic flow velocity, and diastolic flow velocity before and after surfactant instillation regardless of gestational age. Individual changes in mean CBFV were related to MBP changes (p < 0.001, linear mixed models with random effects). CONCLUSION: In low birth weight infants with RDS, bovine surfactant instillation is not associated with a significant alteration in cerebral hemodynamics. However, the direct relationship between CBFV and MBP is consistent with the reported pressure-passive cerebral circulation in sick preterm infants.

Purine in bronchoalveolar lavage fluid as a marker of ventilation-induced lung injury.

To investigate in a rat model of ventilation-induced lung injury whether metabolic changes in the lung are reflected by an increased purine concentration (adenosine, inosine, hypoxanthine, xanthine, and urate; an index of adenosine-triphosphate breakdown) of the bronchoalveolar lavage fluid and whether purine can, thus, indirectly serve as a marker of ventilation-induced lung injury. Prospective, randomized, controlled trial. Research laboratory. Forty-two male Sprague-Dawley rats. Five groups of Sprague-Dawley rats were subjected to 6 mins of mechanical ventilation. One group was ventilated at a peak inspiratory pressure of 7 cm H2O and a positive end-expiratory pressure of 0 cm H2O. A second group was ventilated at a peak inspiratory pressure of 45 cm H2O and a positive end-expiratory pressure of 10 cm H2O. Three groups of Sprague-Dawley rats were ventilated at a peak inspiratory pressure of 45 cm H2O without positive end-expiratory pressure. Before mechanical ventilation, two of these groups received intratracheal administration of saline or exogenous surfactant at a dose of 100 mg/kg and one group received no intratracheal administration. A sixth group served as the nonventilated controls. Bronchoalveolar lavage fluid was collected in which both purine concentration (microM; mean +/- SD) and protein concentration (mg/mL; mean +/- SD) were determined. Statistical differences were analyzed using the one-way analysis of variance (ANOVA) with a Student-Newman-Keul's post hoc test. Purine and protein concentrations were different between groups (ANOVA p value for purine and protein, <.0001). Both purine and protein concentrations in bronchoalveolar lavage fluid were increased in Group 45/0 (3.2 +/- 1.9 and 4.2 +/- 1.6, respectively) compared with Group 7/0 (0.4 +/- 0.1 [p < .05] and 0.4 +/- 0.2 [p < .001]) and controls (0.2 +/- 0.2 [p < .01] and 0.2 +/- 0.1 [p < .001]) and in Group 45/Na (5.8 +/- 2.5 and 4.2 +/- 0.5) compared with Group 7/0 (purine and protein, p < .001) and the controls (purine and protein, p < .001). Positive end-expiratory pressure prevented an increase in purine and protein concentrations in bronchoalveolar lavage fluid (0.4 +/- 0.3 and 0.4 +/- 0.2, respectively) compared with Group 45/0 (purine, p < .01; protein, p < .001) and Group 45/Na (purine and protein, p < .001). Surfactant instillation preceding lung overinflation reduced purine and protein concentration in bronchoalveolar lavage fluid (2.1 +/- 1.6 and 2.7 +/- 1.0) compared with Group 45/Na (purine, p < .001; protein (p < .01). Surfactant instillation reduced protein concentration compared with Group 45/0 (p < .01). This study shows that metabolic changes in the lung as a result of ventilation-induced lung injury are reflected by an increased level of purine in the bronchoalveolar lavage fluid and that purine may, thus, serve as an early marker for ventilation-induced lung injury. Moreover, the study shows that both exogenous surfactant and positive end-expiratory pressure reduce protein infiltration and that positive end-expiratory pressure decreases the purine level in bronchoalveolar lavage fluid after lung overinflation.

Surfactant nebulization versus instillation during high frequency ventilation in surfactant-deficient rabbits.

Surfactant nebulization improves lung function at low alveolar doses of surfactant. However, efficiency of nebulization is low, and lung deposition seems to depend on lung aeration. High frequency ventilation (HFV) has been shown to improve lung aeration. We hypothesize that the combination of HFV and surfactant nebulization may benefit lung deposition of surfactant and consequently, lung function. The aim of this study was to compare the effect of surfactant nebulization versus instillation during HFV on lung function, surfactant distribution, and cerebral blood flow. Therefore, severe respiratory failure was induced by lung lavages in 18 rabbits. HFV was applied: frequency = 8 Hz, mean airway pressure = 12 cm H2O, amplitude = 100%, fraction of inspired O2 = 1.0. Technetium-99m-labeled surfactant (Alveofact, 100 mg/kg of BW) was nebulized or instilled (n = 6 each). Six other rabbits did not receive surfactant (control, HFV only). We found that after instillation partial arterial O2 tension increased from 7.0 kPa (95% confidence interval, 6.3-8.0 kPa) to 34 kPa (16-51 kPa), and during nebulization from 7.0 kPa (6.0-9.0 kPa) to 46 kPa (27-58 kPa). Partial arterial CO2 tension decreased after instillation from 6.1 kPa (5.3-7.1 kPa) to 4.8 kPa (3.9-5.6 kPa), and during nebulization, after an initial rise, it decreased from 6.3 kPa (5.3-7.4 kPa) to 4.9 kPa (4.4-5.6 kPa). Both treatments resulted in nonuniform distribution. Surfactant deposition after nebulization was 9.8%. Instillation resulted in a drop of mean arterial blood pressure of 17% (8-31%), and an even more pronounced drop in cerebral blood flow of 39% (18-57%). Nebulization did not affect blood pressure. Cerebral blood flow decreased with a maximum of 27% (10-37%). We conclude that surfactant nebulization during HFV improves lung function in rabbits with severe respiratory failure, without improving distribution, but with less effects on blood pressure and cerebral blood flow, when compared with surfactant instillation.

Effect of surfactant on respiratory failure associated with thoracic aneurysm surgery

To study the effects of surfactant administration on the left lung after surgical repair of descending aortic aneurysms on postoperative respiratory failure. Randomized, prospective, controlled study. Clinical investigation. Eleven patients with respiratory failure associated with thoracic aneurysm surgery. Eleven adult patients with acute respiratory failure (PaO2/FIO2 <300 torr [<40 kPa]) after surgical repair of descending aortic aneurysms. The artificial surfactant (30 mg/kg) was given to the operated side of the lung by intrabronchial instillation in six patients (surfactant group), whereas nothing was instilled in the other five patients (control group). Hemodynamic parameters, blood gas, and peak inspiratory pressure were measured at the end of surgery, before surfactant instillation, and at 2, 6, 12, 24, and 48 hrs after surfactant instillation. At the end of surgery, the mean +/- SEM values of the PaO2/FIO2 ratio were 204 +/- 25 torr (27.2 +/- 3.3 kPa) in the surfactant group and 240 +/- 26 torr (32.0 +/- 3.5 kPa) in the control group. After 2, 6, 12, and 48 hrs, improvements in the PaO2/FIO2 ratios were observed in the surfactant group, whereas the control group showed no improvement. Two hours after surfactant instillation, the mean value in the PaO2/FIO2 ratio was significantly higher in the surfactant group (318 +/- 24 torr [42.4 +/- 3.2 kPa]) (p < .05) compared with the control group values (240 +/- 34 torr [32 +/- 4.5 kPa]). Surfactant administration immediately after surgery restored gas exchange in postoperative respiratory failure associated with thoracic aneurysm surgery.

Meniscus formation during tracheal instillation of surfactant.

The method of surfactant instillation into the lungs for treatment of neonatal respiratory distress syndrome is an important attribute of delivery, and it may determine the overall efficacy of treatment. Previous studies primarily focused on the rate at which the bolus is instilled. These findings show that rapid injections lead to a more homogenous distribution, whereas slow infusions drain into the dependent lung with respect to gravity, resulting in a heterogeneous deposition. These results suggest that it is beneficial to form a meniscus, from which a more homogenous dispersal can proceed. The objective of the present study was to develop a functional criterion for meniscus formation during bolus injection. An in vitro experiment was used to examine the clinical setting of surfactant instillation. The physical variables examined were the bolus viscosity (mu) and density (rho), gravity (g), injection rate (Q), orientation of the trachea with respect to gravity (theta), tracheal size (D), surface tension (gamma), and catheter size (d). All quantities were varied, except gravity and catheter size. Experimental results show that a meniscus will form when NSt > 0. 004Re2/3, where NSt is Stokes number and Re is Reynolds number, NSt = muQ/D4rhogsintheta, a ratio of viscous effects to gravitational effects, and Re = rhoQD/d2mu, a ratio of inertial effects to viscous effects. Rapid injections, high viscosity, and small inclination with respect to gravity promote meniscus formation. These results can be used to refine the guidelines for administration of surfactant replacement therapy.

Protein composition of synthetic surfactant affects gas exchange in surfactant-deficient rats.

Synthetic surfactant peptides offer an opportunity to standardize the protein composition of surfactant. We tested the effect of phospholipids (PL) with synthetic full-length SP-B1-78 (B), mutant B (Bser), KL4 peptide (UCLA-KL4), and palmitoylated SP-C1-35 (C) on oxygenation and lung function in a surfactant-deficient rat model. Sixty-four adult rats were ventilated with 100% oxygen, a tidal volume of 7.5 mL/kg, and a rate of 60/min. Their lungs were lavaged with saline until the arterial PO2 dropped below 80 torr, when 100 mg/kg surfactant was instilled. Surfactant preparations included: PL (PL surfactant), PL + 3% B (B surfactant), PL + 3% B and 1% C (BC surfactant), PL + 3% UCLA-KL4 (KL4 surfactant), PL + 3% Bser (Bser surfactant), and PL + 3% B and 1% UCLA-KL4 (BKL4 surfactant). Sixty minutes after surfactant instillation, positive end-expiratory pressure was applied for 5 min, and pressure-volume curves were determined in situ. The six surfactant preparations had a minimum surface tensions <10 mN/m on a Langmuir/Wilhelmy balance. Instillation of PL, Bser, and BKL4 surfactant increased mean arterial/alveolar PO2 (aADO2) ratios by 50-100% over postlavage values, whereas KL4 surfactant increased aADO2 ratios by 118%, B surfactant by 191%, and BC surfactant by 225%. Lung volumes at 30 cm H2O pressure were highest after treatment with BC surfactant, intermediate after B and KL4 surfactants, and lowest after BKL4, Bser, and PL surfactants. These data suggest that a surfactant preparation with a combination of synthetic B and C peptides surpasses synthetic B and KL4 surfactants in improving oxygenation and lung compliance in surfactant-deficient rats.

Lung Trauma From Five Moderately Large Manual Inflations Immediately After Surfactant Instillation in Newborn Immature Lambs † 1678

Lung Trauma From Five Moderately Large Manual Inflations Immediately After Surfactant Instillation in Newborn Immature Lambs † 1678

Surfactant nebulisation prevents the adverse effects of surfactant therapy on blood pressure and cerebral blood flow in rabbits with severe respiratory failure

Surfactant replacement therapy for the neonatal respiratory distress syndrome has shown beneficial effects on lung function and survival. Recently, rapid fluctuations of haemodynamics and cerebral perfusion following surfactant instillation have been described and an association with the development of intraventricular haemorrhage has been proposed. Therefore, alternative methods of surfactant therapy that reduce the effects on cerebral perfusion have to be explored. Does instillation of surfactant influence blood pressure and cerebral blood flow in rabbits with severe respiratory failure? Can nebulisation of surfactant prevent these adverse effects on blood pressure and cerebral blood flow? Surfactant (Alveofact, 100 mg/kg body weight) was nebulised using the MiniNEB nebuliser, or instilled, in 12 rabbits with severe respiratory failure induced by lung lavage. Assessed were blood gasses, mean arterial blood pressure (MABP) and cerebral blood flow over the left carotid artery, using ultrasonic transit-time flow probes. Partial pressure of oxygen in arterial blood increased quickly after instillation, from 8.7 +/- 1.3 to 24.9 +/- 6.4 kPa after 15 min, and increased gradually during nebulisation from 8.0 +/- 0.5 to 24.5 +/- 4.6 after 120 min. After instillation, MABP decreased 22 +/- 5% (in 8 min) and cerebral blood flow dropped even more: 64 +/- 9% within 8 min. During nebulisation, MABP did not change significantly and cerebral blood flow decreased gradually, 31 +/- 14% over 90 min. Surfactant instillation was followed by a rapid decrease in MABP and an even more pronounced drop in cerebral blood flow, while during nebulisation MABP did not change and cerebral blood flow decreased less and more gradually.