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Spontaneous breathing trials (SBT) can be exhausting, but the preventive role of rest has never been studied. This study aimed to evaluate whether reconnection to mechanical ventilation (MV) for 1 h after the effort of a successful SBT could reduce the need for reintubation in critically ill patients. Randomized multicenter trial conducted in 17 Spanish medical-surgical intensive care units (Oct 2013–Jan 2015). Patients under MV for longer than 12 h who fulfilled criteria for planned extubation were randomly allocated after a successful SBT to direct extubation (control group) or reconnection to the ventilator for a 1-h rest before extubation (rest group). The primary outcome was reintubation within 48 h. Analysis was by intention to treat. We recruited 243 patients randomized to the control group and 227 to the rest group. Median time from intubation to SBT did not differ between groups [5.5 (2.7, 9.6) days in the control group vs. 5.7 (2.7, 10.6) in the rest group; p = 0.85]. Reintubation within 48 h after extubation was more common in the control than in the rest group [35 (14%) vs. 12 (5%) patients; OR 0.33; 95% CI 0.16–0.65; p

To determine the effects of deflating the tracheal cuff during disconnections from mechanical ventilation (MV) in tracheostomized patients. This was a single-center, randomized trial conducted in a general ICU of a tertiary hospital with regional referral for trauma patients. Patients at high risk of aspiration based on the drink test were excluded. Critically ill tracheostomized patients were randomized to have the tracheal cuff deflated or not during spontaneous breathing trials. Weaning was protocolized on progressive T-tube trials, and patients were considered weaned after 24 consecutive hours disconnected from MV. The primary end point was time to definitive withdrawal of MV; secondary end points were ventilator-associated respiratory infection (pneumonia and/or tracheobronchitis) and swallowing function. Statistical analyses included Cox proportional risk models. We randomized 195 patients and 181 patients completed the study (94 patients with deflated cuff and 87 with inflated cuff). Variables independently related to weaning time in the multivariate analysis were tracheostomy-to-first MV disconnection time (HR 0.5, 95 % CI 0.3–0.8; p

Although low doses of oxygen (FiO20.50) are considered nontoxic, recent studies have shown that even lower doses increase pulmonary inflammatory mediators. We aimed to evaluate the acute effects of reducing FiO2 on pulmonary inflammation in mechanically ventilated patients without respiratory failure.This study was a prospective, single-center crossover study in a medical/surgical intensive care unit at a university hospital. Hemodynamically stable patients under mechanical ventilation for24 h without severe respiratory failure (PaO2/FiO2250). A basal FiO2 of 0.40 was reduced to 0.21 provided SpO2 remained higher than 90 %. Patients who could not tolerate the reduction in FiO2 to 0.21 were excluded.We screened 40 patients, but only 28 (70 %) tolerated FiO2 0.21. We measured common clinical variables and inflammatory mediators in plasma and in exhaled breath condensate (EBC) at the end of three 4-h periods: (1) basal (FiO2 0.40), (2) after FiO2 reduction to 0.21, and (3) after returning FiO2 0.40. We used one-way ANOVA for repeated measurements with FiO2 as the grouping variable. Median values of inflammatory mediators in EBC showed nonsignificant changes among the three periods: NO2 + NO3 17.1, 14.1 and 11.0 μmol/L (p = 0.2), and 8-isoprostane 4.4, 8.2 and 5.3 pg/ml (p = 0.6) for the three periods, respectively. Plasma levels also showed nonsignificant changes during the period of the study: NO2 + NO3 12.6, 16.3 and 15.0 μmol/L (p = 0.9), TNFα 13.5, 18.0 and 14.5 pg/ml (p = 0.8), IL-4 12.9, 18.7 and 23.9 pg/ml (p = 0.1), IL-6 50.9, 35.1 and 28.3 pg/ml (p = 0.6), and IL-10 15.2, 22.2 and 22.2 pg/ml (p = 0.7) for the three periods, respectively.FiO2 0.40 in mechanically ventilated patients without severe respiratory failure did not increase systemic or pulmonary inflammation.

Background: Prone position ventilation for acute hypoxemic respiratory failure (AHRF) improves oxygenation but not survival, except possibly when AHRF is severe. Objective: To determine effects of prone versus supine ventilation in AHRF and severe hypoxemia [partial pressure of arterial oxygen (PaO 2)/inspired fraction of oxygen (FiO2)

To determine the effect of discharge from the ICU with a tracheostomy tube on ward mortality and its relation to patient vulnerability.Retrospective single-center cohort study.Database (2003-2006) review of patients undergoing mechanical ventilation (MV)24 h and discharged from the ICU with or without tracheostomy tube in place and followed up to hospital discharge or death. We recorded clinical characteristics, complications, major ICU procedures, subjective prognosis at ICU discharge (Sabadell score), and hospital outcome. Factors associated with ward mortality were analyzed by multiple logistic regression.From 3,065 patients admitted to the ICU, 1,502 needed MV24 h. Only 936 patients (62%) survived the ICU and were transferred to the ward; of these, 130 (13.9%) had a tracheostomy tube in place. Ward mortality was higher in patients with a tracheostomy tube in place than in those without (26 vs. 7%, P0.001). Increased ward mortality among cannulated patients was seen only in those with intermediate Sabadell score (24 vs. 9% in score 1, P = 0.02, and 38 vs. 24% in score 2, P = 0.06), but not in the "good prognosis" (2 vs. 2%, score 0) and "expected to die in hospital" (80 vs. 75%, score 3) groups. Multivariate analysis found three factors associated with ward mortality: age, tracheostomy tube in place, and Sabadell score.Lack of tracheostomy decannulation in the ICU appears to be associated with ward mortality, but only in the group with a Sabadell score of 1.

Examine the impact of previous statin therapy on hospital mortality and whether it is due to a protective effect against ICU-acquired infections.Cohort comparison study by retrospective chart-based analysis in a 26-bed, university-affiliated, medical-surgical ICU.We analyzed data from 438 patients at high risk of ICU-acquired infections, i.e., those receiving mechanical ventilation for more than 96 h, 38 (8.7%) of whom had been treated with statins prior to and during ICU admission.We recorded clinical characteristics, number and type of ICU-acquired infections, and ICU and hospital mortality. Statin-treated patients were older (71.7+/-8.3 vs. 61.5+/-18.3 years), but differences in predicted mortality risk by APACHE II (39.5+/-24.7 vs. 35.8+/-24.3%) did not reach statistical significance. The ICU-acquired infection rate in statin-treated patients was nonsignificantly lower (29% vs. 38%) and delayed (median 12 vs.10 days), without differences regarding the source of infections. Nevertheless, hospital mortality was significantly higher in statin-treated patients (61% vs. 42%), even after adjustment for APACHE II predicted risk (observed/expected ratio 1.53 vs. 1.17).Statin therapy is associated with worse outcome, probably because underlying clinical conditions are insufficiently considered in mortality predictors. Its presumed protective effect against ICU infections remains unconfirmed.

This study analyzed the effect of phasic tracheal gas insufflation at mid- to end-expiration in patients with severe head trauma and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).A prospective interventional study in a 16-bed intensive care unit.Seven patients with severe head trauma (Glasgow Coma Scale9) and ALI/ARDS.Patients were ventilated in assist/control mode with a ventilatory strategy providing adequate oxygenation (PaO(2)70 mmHg) and normocapnia (PaCO(2) between 35-40 mmHg). Mid to end expiratory tracheal gas insufflation at 8 l/min flow rate was delivered for 90 min while normocapnia was maintained by simultaneous reductions in tidal volume. We measured (hemodynamics, oxygenation, lung mechanics, and cerebral parameters) in basal situation and during and after tracheal insufflation.Tracheal gas insufflation allowed a significant decrease in tidal volume from 9.1 to 7.2 ml/kg, with associated reduction in driving pressure (plateau pressure minus positive end-expiratory pressure, PEEP) from 18.1 to 13.2 cm H(2)O. Total PEEP increased from 9.3 to 12.7 cm H(2)O due to the generation of lung hyperinflation. Oxygenation improved slightly during tracheal gas insufflation, and this improvement remained after stopping tracheal insufflation. No changes in hemodynamic or cerebral parameters were observed during the study.In patients with severe head trauma and ALI receiving mechanical ventilation, expiratory tracheal gas insufflation allowed the targeted arterial PCO(2) level to be maintained together with a substantial reduction in tidal volume.

Objective. Thermodilution (TD) is the gold standard to monitor cardiac output (CO) in critical care. However, there is concern about the safety of right-ventricular catheterization. The CO2 rebreathing technique allows noninvasive CO determination by means of the indirect Fick principle. Our objectives were: (a) to assess the accuracy of a new system of CO measurement using the CO2 partial rebreathing method (PRCO); (b) to evaluate whether the PRCO itself may induce changes in CO. Design and setting. Prospective study in the intensive care department in a university-affiliated hospital. Patients. Twenty-two mechanically ventilated critically ill patients. Interventions. CO measured simultaneously by PRCO and TDCO. Measurements and results. PRCO and TDCO values were compared by concordance analysis. Stability of cardiac output during PRCO was evaluated by comparing the TDCO measurements before, during, and after the partial rebreathing period using analysis of variance. From a total of 79 valid sets of measurements, bias and precision was calculated at –0.18±1.39 l/min. The concordance analysis of lower and intermediate CO values (

Objective: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). Design: Prospective clinical study. Setting: General intensive care unit in Sabadell, Spain. Patients: Nine mechanically ventilated COPD patients (mean age 72±2 years; forced expiratory volume in 1 s 0.91±0.11 l) and nine ARDS patients (mean age 57±6 years; mean lung injury score 2.8±0.1) Measurements and results: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO2). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO2/FIO2 (fractional inspired oxygen) 190±18 mmHg) than in the ARDS group (PaO2/FIO2 98±12 mmHg), (p

To analyze the clinical and economic consequences of the implementation of a weaning protocol in patients mechanically ventilated (MV) for more than 48 h.Comparative study.General intensive care unit (ICU) in a county hospital covering 360000 inhabitants.51 patients weaned by a fixed protocol were studied prospectively and compared with 50 retrospective controls.The following variables were assessed: Acute Physiology and Chronic Health Evaluation (APACHE) II score, age, cause of respiratory failure, type of extubation (direct extubation or extubation using a weaning technique), number of days on MV before the weaning trial, weaning time, total duration of MV, complications (reintubations and tracheostomies), length of ICU stay, and mortality.The groups were comparable in terms of age, APACHE II score, and main cause of acute respiratory failure. Number of days on MV up to the weaning trial were similar in the two groups (8.4 +/- 7.7 in the protocol group vs 7.5 +/- 5.5 in the control group, NS). Most of the patients (80%) in the protocol group were directly extubated without a weaning technique, unlike the control group (10%) (p0.01). When a weaning technique was used, the weaning time was similar in both groups (3.5 +/- 3.9 days vs 3.6 +/- 2.2 days in the control group). Duration of MV was shorter in the protocol group (10.4 +/- 11.6 days) than in the control group (14.4 +/- 10.3 days) (p0.05). As a result, the ICU stay was reduced by using the weaning protocol (16.7 +/- 16.5 days vs 20.3 +/- 13.2 days in the control group, p0.05). We found no differences in reintubation rate (17 vs 14% in the control group) and need for tracheostomies (2 vs 8% in the control group).The implementation of a weaning protocol decreased the duration of MV and ICU stay by increasing the number of safe, direct extubations.

We examined the effect on survival of prone positioning as an early and continuous treatment in ARDS patients already treated with protective ventilation.Open randomized controlled trial in 17 medical-surgical ICUs.Forty mechanically ventilated patients with early and refractory ARDS despite protective ventilation in the supine position.Patients were randomized to remain supine or be moved to early (within 48[Symbol: see text]h) and continuous (or = 20 h/day) prone position until recovery or death. The trial was prematurely stopped due to a low patient recruitment rate.Clinical characteristics, oxygenation, lung pressures, and hemodynamics were monitored. Need for sedation, complications, length of MV, ICU, and hospital stays, and outcome were recorded. PaO(2)/FIO(2) tended to be higher in prone than in supine patients after 6[Symbol: see text]h (202 +/-78 vs. 165+/-70 mmHg); this difference reached statistical significance on day 3 (234+/-85 vs. 159+/-78). Prone-related side effects were minimal and reversible. Sixty-day survival reached the targeted 15% absolute increase in prone patients (62% vs. 47%) but failed to reach significance due to the small sample.Our study adds data that reinforce the suggestion of a beneficial effect of early continuous prone positioning on survival in ARDS patients.

The static pressure volume (PV) curve of the total respiratory system is a well established method to assess pulmonary mechanics during respiratory failure. We have tested the impact of auto-PEEP on the PV curve determination in 16 COPD patients. An isovolumic pressure increment (IPI) was found at the beginning of the curve and a close correlation between IPI and auto-PEEP level (r = 0.962) p less than 0.001) was observed. The regression equation was not significantly different from the identity line. We conclude that the appearance of IPI in PV curves is largely determined by auto-PEEP and it is a good estimate of the existing auto PEEP level.

We studied airway occlusion pressure (P 0.1) and maximal inspiratory pressure (PIMax) in 10 healthy volunteers (Group A), 10 early postsurgical cardiac patients on spontaneous breathing (Group B), 10 patients mechanically ventilated for ARF (Group C), 10 patients weaning from mechanical ventilation after ARF (Group D) and 10 patients extubated after post-ARF (Group E). We calculated the index P 0.1/PIMax in an attempt to link the ventilatory demands and muscle ventilatory reserve. We found that the sensitivity and specificity in diagnosing the need for either full (C), partial (D) or no ventilatory support (A, B, E) by means of the P 0.1 were C = (50%, 95%), D = (70%, 72%) and A + B + E = (83%, 90%) respectively. When the index P 0.1/PIMax was used they were C = (90%, 100%), D = (80%, 87%) and A + B + E = (86%, 90%). We conclude that the index P 0.1/PIMax increases the reliability of P 0.1 alone to correctly classify the patients that will need either full, partial or no ventilatory support in ARF.

To determine the impact of ventilator-associated pneumonia (VAP) on ICU mortality, and whether it is related to time of onset of pneumonia.Prospective cohort study.16-bed medical-surgical ICU at a university-affiliated hospital.From 2002 to 2003, we recorded patients receiving mechanical ventilation for72 h. Patients developing an infection other than VAP were excluded. Patients definitively diagnosed with VAP (n=40) were cases and patients free of any infection acquired during ICU stay (n=61) were controls. The VAP-attributed mortality was defined as the difference between observed mortality and predicted mortality (SAPS II) on admission.Mechanical ventilation was longer in VAP patients (25 +/- 20 vs 11 +/- 9 days; p0.001), as was ICU stay (33 +/- 23 vs 14 +/- 12 days; p0.001). In the non-VAP group, no difference was found between observed and predicted mortality (27.9 vs 27.4%; p0.2). In the VAP group, observed mortality was 45% and predicted mortality 26.5% (p0.001), with attributable mortality 18.5%, and relative risk (RR) 1.7 (95% CI 1.12-23.17). No difference was observed between observed and predicted mortality in early-onset VAP (27.3 vs 25.8%; p0.20); in late-onset VAP, observed mortality was higher (51.7 vs 26.7%; p0.01) with attributable mortality of 25% and an RR 1.9 (95% CI 1.26-2.63). Empiric antibiotic treatment was appropriate in 77.5% of episodes. No differences in mortality were related to treatment appropriateness.In mechanically ventilated patients, VAP is associated with excess mortality, mostly restricted to late-onset VAP and despite appropriate antibiotic treatment.

Randomized clinical trials demonstrating benefits of noninvasive ventilation (NIV) systematically exclude patients with “do-not-intubate” (DNI) orders, but in daily clinical practice these patients are frequently treated with NIV. A recent North American study found a 43% hospital survival rate in patients with DNI orders. Our hypothesis was that, due to the very different social and cultural setting, written DNI orders in a southern European country would be restricted to a population with a poor outcome, independently of whether they receive NIV, and we analyzed hospital survival in patients receiving NIV and the impact of DNI orders on survival. Retrospective cohort study in a general ICU in a university-affiliated hospital. All 233 patients treated with NIV during 2002–2004. We recorded clinical characteristics on admission, mortality risk by APACHE II and ICU and hospital outcome, and 6-month outcome. Hospital survival was 66%. Survival was better in the 199 patients without DNI orders than in the 36 with DNI orders both during hospitalization (74% vs. 26%, OR 7.9) and after 6 months (64% vs. 15%, OR 10.2). In both groups the presence of COPD was associated with better prognosis during hospitalization, but not in the medium-term. Our study suggests that NIV offers low expectations for medium-term survival in DNI patients.

To compare changes in lung volume, oxygenation, airway pressure, and hemodynamic effects induced by suctioning with three systems in critically ill patients with mild-to-moderate lung disease, and also to evaluate the effects of hyperoxygenation applied prior to the maneuver as suggested by some guidelines.Prospective crossover study.General intensive care department of a university-affiliated hospital.Ten mechanically ventilated patients with mild-to-moderate acute respiratory failure.Patients were ventilated in volume control mode with a mean tidal volume of 490+/-88 ml, PEEP 7+/-4 cmH2O and FiO(2) 0.36+/-0.05. Suctioning was performed sequentially with a quasi-closed system, with an open system 10 min later, and finally with a closed system. Thereafter, pure oxygen was applied for 2 min and the whole suctioning sequence was repeated in reverse order.Patients' mean PaO(2)/FiO(2) ratio was 273+/-28 mmHg. The reductions in lung volume during suctioning were similar with the quasi-closed (386+/-124 ml) and closed system (497+/-338 ml), but significantly higher with the open system (1281+/-656 ml, P=0.022). We found no significant hemodynamic adverse effects, and no significant SpO(2) reductions with all the studied suctioning techniques. Pre-oxygenation with pure oxygen did not induce additive effects in lung volume changes. With and without pre-oxygenation, lung volume returned to baseline in every patient within 10 min.Suctioning with closed and quasi-closed systems reduces the substantial losses in lung volume observed with the open system. Nevertheless, in patients without severe lung disease these changes were transient and rapidly reversible.

To evaluate the ability of the new, built-in occlusion pressure (P0.1) measurement to predict extubation failure. Prospective observational multicentre study in the ICU of five general hospitals. Hundred thirty patients on mechanical ventilation longer than 48 h when considered ready for weaning. Patients underwent a 30-min spontaneous breathing trial with simultaneous monitoring of occlusion pressure (P0.1) and breathing pattern (f/Vt). Sixteen patients (12%) failed the weaning trial and full ventilatory support was resumed, while 114 tolerated the trial and were extubated. Twenty-one (18%) required reintubation within 48 h. The area under the ROC curve for diagnosing extubation failure was 0.53 for f/Vt, 0.59 for P0.1 and 0.61 for P0.1*f/Vt (p=NS). Accordingly, P0.1*f/Vt more than 100 detected extubation failure with a sensitivity of 0.89, specificity of 0.35, positive predictive value of 0.21 and negative predictive value of 0.94. During a first trial of spontaneous breathing on pressure support ventilation (PSV), bedside P0.1 and P0.1*f/Vt are of little help, if any, for predicting extubation failure.

OBJECTIVE To evaluate the relationship between PaCO2 and end-tidal CO2 tension (PetCO2) before weaning and during a weaning trial and to determine the ability of PetCO2 to identify clinically relevant episodes of hypercapnia. DESIGN: Open, prospective study. SETTING: General intensive care unit. PATIENTS: 30 critically ill patients (mean age 63 +/- 2 years; Acute Physiology And Chronic Health Evaluation (APACHE) II of 18.4 +/- 3) who underwent a weaning trial during the recovery phase of acute respiratory failure requiring mechanical ventilation (MV) (8.9 +/- 1 days on MV). INTERVENTIONS: Weaning trial consisted of 2 h breathing on 5 cmH2O of Continuous Positive Airway Pressure (CPAP). MEASUREMENTS AND RESULTS: Arterial blood gas values, PetCO2 register and pulse oximetry determinations were recorded in assist/control ventilation before CPAP, after 1 h on CPAP and after 2 h on CPAP (immediately before extubation) or immediately before returning to assist/control mode in patients who failed the weaning trial. Clinically relevant hypercapnic episodes were described as: (1) an increment in PaCO2 > 42 mm Hg in previously normocapnic patients and (2) an increment of > 8 mm Hg from previous PaCO2 in previously hypercapnic patients. Changes in PaCO2 and changes in PetCO2 between MV and the first and second hour of CPAP showed a significant correlation (r = 0.74; p < 0.01). Clinically relevant hypercapnic episodes were detected by increments of > 3 mm Hg in PetCO2 with a sensitivity of 82%, a specificity of 76% and a negative predictive value of 94%. The area under the receiver operating characteristic curve for increments in PetCO2 was 0.90. CONCLUSIONS: Capnography provided good assessment of hypercapnic episodes during weaning, although the high number of false positives may result in arterial blood sampling in patients who do not present with ventilation failure.

Objective: Inhaled nitric oxide (NO) and prone position improve arterial oxygenation in patients with the acute respiratory distress syndrome. This study was undertaken to assess the combined effects of NO and prone position in these patients. Design: Prospective clinical study. Setting: General intensive care service in a community teaching hospital. Patients: 14 mechanically ventilated adult patients with the acute respiratory distress syndrome (mean lung injury score 3.23 ± 0.27). Measurements and results: We measured hemodynamic and oxygenation parameters in the supine position and 2 h later in the prone position, before and during inhalation of 10 ppm NO. A positive response in oxygenation was defined as a ≥ 20 % increment in the arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2). In the prone position PaO2/FIO2 increased significantly (from 110 ± 55 to 161 ± 89 mmHg, p < 0.01) and venous admixture decreased (from 38 ± 12 to 30 ± 7 %, p < 0.01) compared to the supine position. Ten of the 14 patients were responders in the prone position. In the supine position, inhalation of NO improved oxygenation to a lesser extent, increasing PaO2/FIO2 to 134 ± 64 mmHg (p < 0.01) and decreasing venous admixture to 35 ± 12 %, (p < 0.01). Five of the 14 patients responded to NO inhalation supine and 8 of 14 responded prone (p = 0.22). The combination of NO therapy and prone positioning was additive in increasing PaO2/FIO2 (197 ± 92 mmHg) and decreasing venous admixture (27 ± 8 %) (p < 0.01). This combination also showed a positive oxygenation response on compared to the supine value without NO in 13 of the 14 patients (93 %). NO-induced changes in PaO2/FIO2 were correlated to changes in pulmonary vascular resistance only in the prone position. Conclusions: In patients with the acute respiratory distress syndrome, the combination of NO and prone position is a valuable adjunct to mechanical ventilation.

To assess the accuracy of static pressure-volume (PV) curves of the total respiratory system performed with the data directly obtained from the Servo 900C vs. the data obtained from an external calibrated device. Performance of the PV curve by the method of Levy with simultaneous recording of data obtained from both systems. The general ICU of Hospital de Sabadell. Ten sedated and paralyzed patients ventilated in the control mode for acute respiratory failure were evaluated. Inflation static PV curves were performed by the method of Levy. We simultaneously measured airway pressure and volume by means of calibrated pressure tranducer and pneumotachograph and by the internal devices built in the ventilator Siemens Servo 900C. Statistics were concordance analysis between the two methods and covariance analysis between derived curves. concordance analysis between both methods showed a 95% confidence interval of (+4%, −5%) in volume and (+2.2 cmH2O, −1.7 cmH2O) in pressure. Derived PV curves analyzed by MANOVA showed no significant differences whichever the method used within subject (p=0.579). Inflation static pressure volume curves of the total respiratory system can be accurately performed with the data directly obtained from the Servo Ventilator 900C without the need of any other external device.

Gentamicin intrapatient pharmacokinetics variations were studied in 40 critically ill medical patients, suffering gram-negative sepsis. These patients were studied in two phases throughout gentamicin treatment: firstly, on the second day of treatment, when aggressive fluid therapy was required, and secondly, five days later, when patients had achieved a more stable clinical condition. Pharmacokinetic parameters were determined using least squares linear regression analysis assuming a one-compartment model using the Sawchuk-Zaske method. The apparent volume of distribution (Vd) in the first phase of the study was 0.43 +/- 0.12 L/kg, while on the seventh day of treatment it was 0.29 +/- 0.17 L/kg (p less than 0.001). Statistically significant differences were also observed for peak serum concentration (p less than 0.001), total dosage recommended (p less than 0.001) and half-life (p less than 0.05), whilst differences were not found for trough levels. From the analysis of the results obtained, we recommend increasing the initial dosage and monitoring plasma levels within the first days of therapy in critically ill patients treated with gentamicin, since important variations in aminoglycoside Vd related to disease, fluid balance and renal function, commonly occur in these patients.

We have studied eleven patients ventilated in the assisted mode during recovery from acute respiratory failure. We have measured the effort required to trigger the pressure demand valve for 3 different ventilators, and have measured the occulusion pressure as an index of neuromuscular inspiratory drive. We found a delay in the opening of the demand valve, as previously described by other authors. We also found a close correlation between the effort required to open the demand valve and the occlusion pressure. We conclude that the inspiratory effort required to open the demand valve, in the assist mode, is greater than the preset trigger level and that it is well correlated with the neuromuscular inspiratory drive. This inspiratory effort against the closed demand valve, allows the measurement of the occlusion pressure.