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Nebulized amikacin may be an attractive option for the treatment of lung infections. Low systemic absorption may permit the use of high doses, leading to high lung concentrations without systemic toxicity. We evaluated the pharmacokinetics and safety of an optimized high-dose amikacin nebulization technique. in vitro and in vivo pharmacokinetic study. Six healthy volunteers (age 21–30 years, weight 49–68 kg). The Aeroneb Pro nebulizer with an Idehaler vertical spacer was evaluated in a bench study. Amikacin was administered intravenously (15 mg/kg) and nebulized (40, 50, and 60 mg/kg) during noninvasive pressure-support ventilation through a mouthpiece. Median (interquartile range) in vitro inhaled fraction was 31% (30–32) and inhalable output was 681 mg/h (630–743). Serum concentrations after nebulization were less than or equal to those after infusion. The area under the serum concentration curve was significantly higher after infusion (138 mg h–1l–1, 122–143) than after nebulization (49 mg h–1l–1, 39–55, at 40 mg/kg; 63, 53–67 at 50; 66, 50–71, at 60). Peak serum concentration was also higher after infusion: 48 mg/l (45–49) after infusion compared to 8.2 (5.6–8.7), 9.2 (7.6–10.2), and 9.2 (5.2–10.3), respectively. Mean absorption times after nebulization were 2 h 24 min (2,07–2,45), 2 h 21 min (2,07–2,35), and 2 h 5 min (2,00–2,25), respectively. No side effect was observed. Nebulization of up to 60 mg/kg amikacin appears to be safe in healthy subjects and associated with lower serum concentrations than a 15 mg/kg infusion. [ABSTRACT FROM AUTHOR]

To avoid ventilator induced lung injury, tidal volume should be low in acute lung injury (ALI). Reducing dead space may be useful, for example by using a pattern of inspiration that prolongs the time available for gas distribution and diffusion within the respiratory zone, the mean distribution time (MDT). A study was conducted to investigate how MDT affects CO2 elimination in pigs at health and after ALI. Randomised crossover study in the animal laboratory of Lund University Biomedical Center. Healthy pigs and pigs with ALI, caused by surfactant perturbation and lung-damaging ventilation were ventilated with a computer-controlled ventilator. With this device each breath could be tailored with respect to insufflation time and pause time ( T I and T P) as well as flow shape (square, increasing or decreasing flow). The single-breath test for CO2 allowed analysis of the volume of expired CO2 and the volume of CO2 re-inspired from Y-piece and tubes. With a long MDT caused by long T I or T P, the expired volume of CO2 increased markedly in accordance with the MDT concept in both healthy and ALI pigs. High initial inspiratory flow caused by a short T I or decreasing flow increased the re-inspired volume of CO2. Arterial CO2 increased during a longer period of short MDT and decreased again when MDT was prolonged. CO2 elimination can be enhanced by a pattern of ventilation that prolongs MDT. Positive effects of prolonged MDT caused by short T I and decreasing flow were attenuated by high initial inspiratory flow. [ABSTRACT FROM AUTHOR]

Prognosis of patients with ischemic stroke requiring mechanical ventilation (MV) has been reported to be poor. However, longterm survival and functional outcome have scarcely been studied and nothing is known about the prevalence of cognitive impairment or depression in survivors and their quality of life (QoL). We identified all patients treated for acute ischemic stroke on a Neurological Intensive Care Unit during 3.5 years who required MV for more than 24 hours. Early mortality rate at 2 months and survival rates at 1 and 2 years were determined. Survivors were examined for functional outcome (modified Rankin Scale (mRS), Barthel Index), cognitive impairment (Mini Mental State Examination (MMSE)), depression (Beck Depression Inventory, BDI) and QoL (Short Form–36). Clinical characteristics on admission were analyzed for prognostic significance. Of 101 consecutive patients, 44% died within 60 days. Survival rates at 1 and 2 years were 40% and 33%, respectively.Age > 60 years (p = 0.002) and Glasgow Coma Scale score < 10 on admission (p = 0.002) were independent predictors of early and late mortality. History of myocardial infarction (p = 0.007) independently predicted late mortality at 2 years. Of 33 surviving patients, nine (27%) had a good functional outcome (mRS 0–2). Of 27 survivors who could be interviewed, 17 (63%) had no cognitive impairment (MMSE > 24) and 20 (74%) did not suffer from relevant depression (BDI < 19). In conclusion, longer–term survival of patients with ischemic stroke requiring MV was 33% and every fourth survivor resumed an independent life without dementia or depression. Older patients comatose on admission and with concomitant cardiovascular disease had the lowest probability of a favorable outcome. [ABSTRACT FROM AUTHOR]

Objective: Invasive aspergillosis is associated with a poor prognosis, especially in critically ill patients with cerebral involvement. We present two cases of cerebral invasive aspergillosis successfully treated in the intensive care unit with combination antifungal therapies and without surgery.Case Presentation: The first patient was a 49-year-old man with rheumatoid arthritis who received corticosteroid and cyclophosphamide treatment and developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole the patient had a successful outcome with voriconazole and liposomal amphotericin B therapy. The patient returned home after an 8-month hospital stay. The second patient was a 54-year-old woman with pulmonary neoplasia and corticosteroid treatment who developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole and liposomal amphotericin B therapy the patient had a favorable outcome with liposomal amphotericin B and caspofungin therapy. The patient died 10 months after initial diagnosis of cardiac tamponade unrelated to fungal infection.Discussions: These cases illustrate the improving prognosis of invasive aspergillosis due to the availability of new treatments, especially in cases of cerebral involvement. It also demonstrates that the outcome of critically ill patients requiring mechanical ventilation for invasive aspergillosis can be favorable. The treatment of patients with invasive cerebral aspergillosis in the intensive care setting should be encouraged. [ABSTRACT FROM AUTHOR]

Objective: Use of lung-protective mechanical ventilation (MV) by applying lower tidal volumes is recommended in patients suffering from acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Recent data suggest that lung-protective MV may benefit non-ALI/ARDS patients as well. This study analyzed tidal volume settings in three ICUs in The Netherlands to determine the effect of feedback and education concerning use of lung-protective MV.Design and Setting: Observational study in one academic and two nonacademic "closed format" ICUs.Patients: Intubated mechanically ventilated subjects.Interventions: Feedback and education concerning lung-protective MV with special attention to the importance of closely adjusting tidal volumes to predicted body weight (PBW).Results: Tidal volumes declined significantly within 6 months after intervention (from 9.8+/-2.0 at baseline to 8.1+/-1.7 ml/kg PBW) as the percentage of undesirable ventilation data points, defined as tidal volumes greater than 8 ml/kg PBW (84% vs. 48%). There were no differences between patients meeting the international definition criteria for ALI/ARDS and those not. Only four patients received tidal volumes less than 6 ml/kg PBW. Lower tidal volumes were still used after 12 months. Tidal volumes in patients on mandatory MV and patients breathing on spontaneous modes were similar.Conclusions: Feedback and education improve physician compliance in use of lung-protective MV. [ABSTRACT FROM AUTHOR]

Objective: Measurements from the pulmonary pressure-volume (PV) curve have been proposed to adjust ventilator settings. We investigated the effects of repeated construction of an inflation PV curve implemented in a standard ventilator on recruitment or derecruitment in acutely injured lungs.Design and Setting: Prospective experimental animal study in eight anesthetized and mechanically ventilated pigs.Interventions: Acute lung injury was induced by lung lavage and animals were ventilated in volume controlled mode with PEEP 10 cmH(2)O. The PV curve was constructed five times repeatedly by constant pressure rise, after which ventilation with the preset PEEP was resumed immediately. Studies of hemodynamics, lung mechanics, blood gases and computed tomography were carried out before and after maneuvers.Measurements and Results: Derecruitment was assessed as an increase in nonaerated lung volume (V(NON)), and V(PEEP) was the end-expiratory volume difference between PEEP and ZEEP. There was a significant decrease in PaO(2) from 90.4+/-33.3 to 70.9+/-36.3 mmHg and a rise in venous admixture from 47.8+/-12.7 to 59.1+/-16.6%. V(PEEP) was reduced from 244 to 202 ml. A corresponding decrease in normally aerated lung volume was observed, while regression analysis revealed increase in V(NON) depending on the amount of preexisting atelectasis.Conclusions: Repeated generation of the PV curve with a readily available tool resulted in worsened oxygenation. Derecruitment of the lungs occurred with loss of PEEP at the start of the maneuver, which could not be recovered by a maximum inflation pressure of 40 cmH(2)O. Repeated use of the investigated tool should be cautioned, and users should consider measures to preserve aerated lung volumes. [ABSTRACT FROM AUTHOR]

Objective: Earlier reports suggested that transthoracic (TTE) determination of the ratio of mitral inflow E wave velocity to early diastolic mitral annulus velocity (E/E') measured by tissue Doppler imaging (TDI) closely approximates PAOP in cardiac patients. However, the value of E/E' for PAOP assessment in ICU patients has not been evaluated. This study assessed whether the E/E' ratio provides an accurate estimation of pulmonary artery occlusion pressure (PAOP) in mechanically ventilated ICU patients.Design and Setting: Prospective, open, clinical study in the ICU of a university hospital.Patients: Twenty-three consecutive mechanically ventilated patients.Interventions: Volume expansion in 14 patients.Measurements and Results: Doppler TTE or TEE mitral inflow and TDI mitral annulus velocities were determined and compared with PAOP measured using a Swan-Ganz catheter. Of all the Doppler variables studied the best correlations were observed between PAOP and the lateral (r=0.84) and medial (r=0.76) annulus E/E' ratio and remained highly significant when the analysis was restricted to TEE (r=0.91 and 0.86) or TTE (r=0.73 and 0.61). The sensitivities and specificities of estimating PAOP at 15 mmHg or higher were, respectively, 86% and 81% for lateral E/E' above 7.5 and 76% and 80% for medial E/E' above 9. PAOP changes after volume expansion (700+/-230 ml) were limited and accurately assessed by repeated E/E' determinations.Conclusions: In mechanically ventilated ICU patients TTE or TEE E/E' determinations using TDI closely approximate PAOP. [ABSTRACT FROM AUTHOR]

Objective: Inhalation of perfluorocarbons (PFC) has been suggested as a new and promising technique of PFC delivery in animal models of severe lung injury. However, no in vitro data were available on the efficacy of PFC aerosolization during mechanical ventilation. Therefore, the aim of the in vitro study was to investigate the influence of physical properties of PFC and the ventilatory settings on the amount of PFC delivered into the lung.Design: In vitro lung model study.Setting: University research laboratory.Measurements and Results: Two different PFC (PF 5080 and PFOB) were aerosolized with a PariBoy jet nebulizer. Using a PFC selective adsorber, the effect of endotracheal tube size (2 mm and 3 mm diameter) on delivery of PFC was investigated. PFC delivery was estimated by continuous measurement of weight gain of the adsorber (adsorption rate). Finally, the influence of respiratory rate and tidal volume on adsorption rate (AR) was studied. AR was significantly reduced by a decreasing tube diameter and ranged from 1.45+/-0.03 ml/min (no tube) to 0.93+/-0.03 ml/min (2.0 mm) for PF 5080 (vapor pressure 51 mmHg) and from 0.49+/-0.06 ml/min to 0.32+/-0.04 ml/min for PFOB (11 mmHg). PFC-aerosolization into a ventilatory circuit with simulation of spontaneous tidal breathing (minute volume 600 ml) reduced AR to 0.16+/-0.02 ml/min. During mechanical ventilation, changes in respiratory rate and tidal volume, which reduce minute ventilation, caused a decrease in AR.Conclusion: The amount of PFC that can be delivered into the lung by aerosolization is very small and is influenced by PFC properties, tube size, and ventilatory settings. [ABSTRACT FROM AUTHOR]

Objective: Tracheal gas insufflation (TGI) reduces PaCO2 by flushing the tracheal and mechanical deadspace, and may have its maximum benefit when TGI gas is unopposed by significant expiratory gas flow. Thus, limiting TGI to the late expiratory period may diminish tracheal exposure to TGI gas while preserving the efficacy of TGI. This study examined the gas exchange consequences of such late-expiratory TGI. Design and setting: Randomized controlled trial, animal study. Materials: Eleven pigs. Interventions: After stable lung injury was established using oleic acid 11 pigs were ventilated using a standardized lung protective strategy. Phasic expiratory TGI was applied for 30 min stages during the last 20%, 40%, 60%, and 100% of expiration in random sequence. PaCO2 was continuously measured via an indwelling blood gas analysis system. Measurements and results: PaCO2 at baseline was 86.1±4.7 mmHg, and decreased progressively with increasing TGI duration of 20%, 40%, and 60%, but not 100%, of expiration (PaCO2=75.7±5.2, 68.8±3.6, 65.1±5.3 and 65.2±5.2 mmHg, respectively). For all stages the reduction in PaCO2 relative to baseline was significant. Trends of increasing PaO2 and airway pressure with increasing TGI duration were noted and most likely associated with a TGI-induced increase in lung volume. Conclusions: Under these conditions confining TGI to the final 60% of expiration achieved effective PaCO2 reduction, not significantly different from panexpiratory TGI, while limiting exposure of the trachea to TGI gas, and reducing the potential for TGI-induced hyperinflation. These findings suggest that TGI is most effectively applied in a phasic manner in late expiration, with its duration titrated to effect. [ABSTRACT FROM AUTHOR]

Objective: The use of respiratory mechanics to optimise ventilator settings has become more common since the integration of pressure and flow transducers into modern ventilators. However, values of respiratory resistance (Rrs) and compliance (Crs) can be overestimated in the presence of tracheal tube leak and clinical decisions based on these figures would be misinformed. This study aimed to assess the influence of tracheal tube leak on measurements of Crs, Rrs and expired tidal volume (VTE) in ventilated children in order to establish when such measurements were reliable in this population. Design: Respiratory function was monitored for at least five consecutive hours during which normal medical procedures were performed. The magnitude and variability of tracheal tube leak was assessed during these periods. Setting: The paediatric and cardiac intensive care units at Great Ormond Street Hospital for Children, NHS Trust, London. Patients: Seventy-five paralysed, fully ventilated infants and children. Results: Ten children had a mean leak greater than 20% (range: 22%–65%). Amongst this group there were wide fluctuations with respect to leak magnitude, VTE, Crs and Rrs. Leaks of less than 20% appeared necessary to obtain reliable measurements of Crs and Rrs and to ensure consistent and adequate ventilation. Conclusions: Leaks larger than 20% result in inconsistent tidal volume delivery and gross overestimation of Crs and Rrs irrespective of ventilation mode. The magnitude of tracheal tube leak needs to be accurately displayed on all ventilatory equipment to verify reliable measures of respiratory function so that appropriate clinical decisions can be made and ventilatory management optimised. [ABSTRACT FROM AUTHOR]