Non-invasive assessment of respiratory muscle activity during pressure support ventilation: accuracy of end-inspiration occlusion and least square fitting methods.

Pressure support ventilation (PSV) should be titrated considering the pressure developed by the respiratory muscles (Pmusc) to prevent under- and over-assistance. The esophageal pressure (Pes) is the clinical gold standard for Pmusc assessment, but its use is limited by alleged invasiveness and complexity. The least square fitting method and the end-inspiratory occlusion method have been proposed as non-invasive alternatives for Pmusc assessment. The aims of this study were: (1) to compare the accuracy of Pmusc estimation using the end-inspiration occlusion (Pmusc,index) and the least square fitting (Pmusc,lsf) against the reference method based on Pes; (2) to test the accuracy of Pmusc,lsf and of Pmusc,index to detect overassistance, defined as Pmusc ≤ 1 cmH2O. We studied 18 patients at three different PSV levels. At each PSV level, Pmusc, Pmusc,lsf, Pmusc,index were calculated on the same breaths. Differences among Pmusc, Pmusc,lsf, Pmusc,index were analyzed with linear mixed effects models. Bias and agreement were assessed by Bland-Altman analysis for repeated measures. The ability of Pmusc,lsf and Pmusc,index to detect overassistance was assessed by the area under the receiver operating characteristics curve. Positive and negative predictive values were calculated using cutoff values that maximized the sum of sensitivity and specificity. At each PSV level, Pmusc,lsf was not different from Pmusc (p = 0.96), whereas Pmusc,index was significantly lower than Pmusc. The bias between Pmusc and Pmusc,lsf was zero, whereas Pmusc,index systematically underestimated Pmusc of 6 cmH2O. The limits of agreement between Pmusc and Pmusc,lsf and between Pmusc and Pmusc,index were ± 12 cmH2O across bias. Both Pmusc,lsf ≤ 4 cmH2O and Pmusc,index ≤ 1 cmH2O had excellent negative predictive value [0.98 (95% CI 0.94-1) and 0.96 (95% CI 0.91-0.99), respectively)] to identify over-assistance. The inspiratory effort during PSV could not be accurately estimated by the least square fitting or end-inspiratory occlusion method because the limits of agreement were far above the signal size. These non-invasive approaches, however, could be used to screen patients at risk for absent or minimal respiratory muscles activation to prevent the ventilator-induced diaphragmatic dysfunction.

Effect of external PEEP in patients under controlled mechanical ventilation with an auto-PEEP of 5 cmH2O or higher.

BACKGROUND: In some patients with auto-positive end-expiratory pressure (auto-PEEP), application of PEEP lower than auto-PEEP maintains a constant total PEEP, therefore reducing the inspiratory threshold load without detrimental cardiovascular or respiratory effects. We refer to these patients as "complete PEEP-absorbers." Conversely, adverse effects of PEEP application could occur in patients with auto-PEEP when the total PEEP rises as a consequence. From a pathophysiological perspective, all subjects with flow limitation are expected to be "complete PEEP-absorbers," whereas PEEP should increase total PEEP in all other patients. This study aimed to empirically assess the extent to which flow limitation alone explains a "complete PEEP-absorber" behavior (i.e., absence of further hyperinflation with PEEP), and to identify other factors associated with it. METHODS: One hundred patients with auto-PEEP of at least 5 cmH2O at zero end-expiratory pressure (ZEEP) during controlled mechanical ventilation were enrolled. Total PEEP (i.e., end-expiratory plateau pressure) was measured both at ZEEP and after applied PEEP equal to 80 % of auto-PEEP measured at ZEEP. All measurements were repeated three times, and the average value was used for analysis. RESULTS: Forty-seven percent of the patients suffered from chronic pulmonary disease and 52 % from acute pulmonary disease; 61 % showed flow limitation at ZEEP, assessed by manual compression of the abdomen. The mean total PEEP was 7 ± 2 cmH2O at ZEEP and 9 ± 2 cmH2O after the application of PEEP (p < 0.001). Thirty-three percent of the patients were "complete PEEP-absorbers." Multiple logistic regression was used to predict the behavior of "complete PEEP-absorber." The best model included a respiratory rate lower than 20 breaths/min and the presence of flow limitation. The predictive ability of the model was excellent, with an overoptimism-corrected area under the receiver operating characteristics curve of 0.89 (95 % CI 0.80-0.97). CONCLUSIONS: Expiratory flow limitation was associated with both high and complete "PEEP-absorber" behavior, but setting a relatively high respiratory rate on the ventilator can prevent from observing complete "PEEP-absorption." Therefore, the effect of PEEP application in patients with auto-PEEP can be accurately predicted at the bedside by measuring the respiratory rate and observing the flow-volume loop during manual compression of the abdomen.

Assessment of Factors Related to Auto-PEEP.

BACKGROUND: Previous physiological studies have identified factors that are involved in auto-PEEP generation. In our study, we examined how much auto-PEEP is generated from factors that are involved in its development. METHODS: One hundred eighty-six subjects undergoing controlled mechanical ventilation with persistent expiratory flow at the beginning of each inspiration were enrolled in the study. Volume-controlled continuous mandatory ventilation with PEEP of 0 cm H2O was applied while maintaining the ventilator setting as chosen by the attending physician. End-expiratory and end-inspiratory airway occlusion maneuvers were performed to calculate respiratory mechanics, and tidal flow limitation was assessed by a maneuver of manual compression of the abdomen. RESULTS: The variable with the strongest effect on auto-PEEP was flow limitation, which was associated with an increase of 2.4 cm H2O in auto-PEEP values. Moreover, auto-PEEP values were directly related to resistance of the respiratory system and body mass index and inversely related to expiratory time/time constant. Variables that were associated with the breathing pattern (tidal volume, frequency minute ventilation, and expiratory time) did not show any relationship with auto-PEEP values. The risk of auto-PEEP ≥5 cm H2O was increased by flow limitation (adjusted odds ratio 17; 95% CI: 6-56.2), expiratory time/time constant ratio <1.85 (12.6; 4.7-39.6), respiratory system resistance >15 cm H2O/L s (3; 1.3-6.9), age >65 y (2.8; 1.2-6.5), and body mass index >26 kg/m(2) (2.6; 1.1-6.1). CONCLUSIONS: Flow limitation, expiratory time/time constant, resistance of the respiratory system, and obesity are the most important variables that affect auto-PEEP values. Frequency expiratory time, tidal volume, and minute ventilation were not independently associated with auto-PEEP. Therapeutic strategies aimed at reducing auto-PEEP and its adverse effects should be primarily oriented to the variables that mainly affect auto-PEEP values.

Cardiac index and oxygen delivery during low and high tidal volume ventilation strategies in patients with acute respiratory distress syndrome: a crossover randomized clinical trial.

INTRODUCTION: The beneficial effect of low tidal volume (TV) ventilation strategy on mortality in patients with acute respiratory distress syndrome (ARDS) has been attributed to the protective effect on ventilator-induced lung injury, and yet its effect on cardiovascular function might also play an important role. The aim of this study was to assess whether low TV ventilation improves cardiac output and oxygen delivery compared with high TV ventilation strategy in patients with ARDS. METHODS: In this crossover randomized clinical trial 16 ARDS patients were recruited in an intensive care unit at a university-affiliated hospital. Each patient was ventilated for 30 min with low (6 mL/kg) and 30 min with high (12 mL/kg) TV. The two experimental periods, applied in random order and with allocation concealment, were separated by 30 min of basal ventilation. Minute ventilation was constantly maintained by appropriate respiratory rate changes. RESULTS: Compared with high TV ventilation, low TV ventilation showed decreased pH (7.37 vs. 7.41, P = 0.001) and increased PaCO2 (49 vs. 43 mmHg; P = 0.002). Cardiac index and oxygen delivery index were increased with low compared with high TV ventilation (3.9 vs. 3.5 L.min⁻¹.m⁻², P = 0.012, and 521 vs. 463 mL.min⁻¹.m⁻², P = 0.002, respectively), while oxygen extraction ratio decreased (0.36 vs. 0.44, P = 0.027). In four patients oxygen extraction ratio was >0.5 during high TV but not during low TV strategy. The magnitude of the change in cardiac index was positively associated with PaCO2 variation (P = 0.004), while it was unrelated to the magnitude of changes in TV and airway pressure. The decrease of cardiac index was predicted by PaCO2 reduction, with and area under ROC curve of 0.72. CONCLUSIONS: Our findings suggest that a low TV ventilation strategy increases cardiac index and oxygen delivery, thus supporting the hypothesis that the beneficial effect of low TV ventilation in patients with ARDS could be partially explained by hemodynamic improvement. In other words, low tidal volume ventilation could be protective also for the cardiovascular system and not only for the lung. The slight increase of PaCO2 during low TV ventilation seems to predict the increase of cardiac index. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00713713.

Prediction of arterial pressure increase after fluid challenge.

BACKGROUND: Mean arterial pressure above 65 mmHg is recommended for critically ill hypotensive patients whereas they do not benefit from supranormal cardiac output values. In this study we investigated if the increase of mean arterial pressure after volume expansion could be predicted by cardiovascular and renal variables. This is a relevant topic because unnecessary positive fluid balance increases mortality, organ dysfunction and Intensive Care Unit length of stay. METHODS: Thirty-six hypotensive patients (mean arterial pressure < 65 mmH) received a fluid challenge with hydroxyethyl starch. Patients were excluded if they had active bleeding and/or required changes in vasoactive agents infusion rate in the previous 30 minutes. Responders were defined by the increase of mean arterial pressure value to over 65 mmHg or by more than 20% with respect to the value recorded before fluid challenge. Measurements were performed before and at one hour after the end of fluid challenge. RESULTS: Twenty-two patients (61%) increased arterial pressure after volume expansion. Baseline heart rate, arterial pressure, central venous pressure, central venous saturation, central venous to arterial PCO2 difference, lactate, urinary output, fractional excretion of sodium and urinary sodium/potassium ratio were similar between responder and non-responder. Only 7 out of 36 patients had valuable dynamic indices and then we excluded them from analysis. When the variables were tested as predictors of responders, they showed values of areas under the ROC curve ranging between 0.502 and 0.604. Logistic regression did not reveal any association between variables and responder definition. CONCLUSIONS: Fluid challenge did not improve arterial pressure in about one third of hypotensive critically ill patients. Cardiovascular and renal variables did not enable us to predict the individual response to volume administration. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00721604.

Remifentanil improves breathing pattern and reduces inspiratory workload in tachypneic patients.

BACKGROUND: Properly titrated opiates decrease respiratory rate but do not affect tidal volume or induce respiratory acidosis. OBJECTIVE: To determine whether remifentanil improves breathing pattern or reduces inspiratory effort in patients with acute respiratory failure and tachypnea or rapid shallow breathing. METHODS: We studied 14 patients who developed tachypnea and/or rapid shallow breathing if the pressure support level was reduced. During pressure support ventilation, each patient received 30-min infusions, separated by 30 min, of remifentanil and placebo. Measurements were obtained before commencing and before stopping each infusion, and after 3 min of unassisted breathing. The main outcomes were rapid shallow breathing index and change in pressure-time product. RESULTS: Remifentanil did not significantly affect tidal volume. During pressure support ventilation, remifentanil infusion reduced respiratory rate, pressure-time product, and cardiovascular double product (heart rate × systolic arterial pressure) without modifying the sedation score. Mean P(aCO(2)) showed a small and clinically negligible increase during remifentanil, but P(aCO(2)) increased more in the hypercapnic patients than in the normocapnic patients. Remifentanil reduced the rapid shallow breathing index after 3 min of unassisted breathing. CONCLUSIONS: Remifentanil improved respiratory pattern and decreased inspiratory muscles effort in patients with tachypnea or rapid shallow breathing, but did not affect oxygenation or sedation. Though the acid-base balance did not show clinically relevant changes on average, we cannot exclude the possibility that remifentanil might prolong weaning in hypercapnic patients. (Clinical-Trials.gov registration NCT00665119.)

Arterial versus plethysmographic dynamic indices to test responsiveness for testing fluid administration in hypotensive patients: a clinical trial.

In the present study, we compared indices of respiratory-induced variation obtained from direct arterial blood pressure measurement with analogous indices obtained from the plethysmogram measured by the pulse oximeter to assess the value of these indices for predicting the cardiac output increase in response to a fluid challenge. Thirty-two fluid challenges were performed in 22 hypotensive patients who were also monitored with a pulmonary artery catheter. Hemodynamic and plethysmographic data were collected before and after intravascular volume expansion. Patients were classified as nonresponders if their cardiac index did not increase by 15% from baseline. Nonresponding patients had both lower arterial pulse variation ([10 +/- 4]% vs [19 +/- 13]%, P = 0.020) and lower plethysmographic pulse variation ([12 +/- 7]% vs [21 +/- 14]%, P = 0.034) when compared with responders. Fluid responsiveness was similarly predicted by arterial and plethysmographic pulse variations (area under ROC curve 0.74 vs 0.72, respectively, P = 0.90) and by arterial and plethysmographic systolic variation (area under ROC curve 0.64 vs 0.72, respectively, P = 0.50). Nonresponders were identified by changes in pulse variation both on arterial and plethysmographic waveform (area under ROC curve 0.80 vs 0.87, respectively, P = 0.40) and by changes in arterial and plethysmographic systolic variations (area under ROC curve 0.84 vs 0.80, respectively, P = 0.76). In the population studied, plethysmographic dynamic indices of respiratory-induced variation were just as useful for predicting fluid responsiveness as the analogous indices derived from direct arterial blood pressure measurement. These plethysmographic indices could provide a noninvasive tool for predicting the cardiac output increase by administering fluid.

Variations in arterial blood pressure and photoplethysmography during mechanical ventilation.

We analyzed ventilation-induced changes in arterial blood pressure and photoplethysmography from waveforms obtained by monitoring 57 patients in the operating room and intensive care unit. Analysis of systolic and pulse pressure variations during positive pressure ventilation, DeltaUp, DeltaDown, and changes in the preejection period on both arterial and photoplethysmographic waveforms were possible in 49 (86%) patients. The pulse pressure variation and preejection period were similar when calculated using both arterial blood pressure and photoplethysmography, whereas the other variables were different. Photoplethysmographic pulse variation >9% identified patients with arterial pulse pressure variation >13% (area under ROC curve = 0.85) or DeltaDown >5 mm Hg (area under ROC curve = 0.85). In hypotensive patients, photoplethysmographic pulse variation >9% remained the best threshold value (pulse pressure variation >13%: area under ROC curve = 0.90; DeltaDown >5 mm Hg: area under ROC curve = 0.93) for predicting fluid responsiveness. In conclusion, this study showed that pulse variations observed in the arterial pressure waveform and photoplethysmogram are similiar in response to positive pressure ventilation. Furthermore, photoplethysmographic pulse variation > 9% identifies patients with ventilation-induced arterial blood pressure variation that is likely to respond to fluid administration.

Norepinephrine and metaraminol in septic shock: a comparison of the hemodynamic effects.

OBJECTIVE: To compare the effects of norepinephrine and metaraminol on hemodynamics in septic shock patients. DESIGN AND SETTING: Open-label, controlled clinical trial in the general intensive care unit of a university-affiliated hospital. PATIENTS AND PARTICIPANTS: Ten consecutive septic shock patients receiving norepinephrine to maintain the mean arterial pressure higher than 65 mmHg. INTERVENTIONS: Patients were monitored with pulmonary artery catheter and indirect calorimetry. At the baseline hemodynamic variables were obtained during norepinephrine infusion. Subsequently norepinephrine was replaced by metaraminol infusion in a dose sufficient to keep mean arterial pressure constant. After 20 min of stable arterial pressure a new set of measurement was repeated. MEASUREMENTS AND RESULTS: Mean arterial pressure did not differ significantly with norepinephrine or metaraminol; there was no relationship between the norepinephrine and metaraminol doses. Replacement norepinephrine with metaraminol did not modify hemodynamic variables; in particular there were no changes in heart rate, stroke volume index, pulmonary artery occlusion pressure, or oxygen consumption index. CONCLUSIONS: This study shows that metaraminol increases arterial pressure as does norepinephrine in septic shock patients. Despite similar effects of norepinephrine and metaraminol, there was no relationship between the dose of the two drugs.

Standard Laryngeal Mask Airway and LMA-ProSeal during laparoscopic surgery.

STUDY OBJECTIVE: To compare the frequency of airway seal and sore throat with the LMA-ProSeal (PLMA) and the standard Laryngeal Mask Airway (LMA) during laparoscopic surgery. DESIGN: Prospective, controlled, randomized, nonblinded clinical study. SETTING: University-affiliated hospital. PATIENTS: 60 adult, ASA physical status I, II, and III patients undergoing laparoscopic surgery with general anesthesia, without contraindication to the use of the laryngeal mask. INTERVENTIONS: Patients were randomized to receive mechanical ventilation [tidal volume (V(T)) 7 mL/kg(-1); positive end-expiratory pressure (PEEP) 10 cmH(2)O] through the PLMA or the standard LMA, both equipped with a gastric tube. MEASUREMENTS: Heart rate, arterial pressure, inspiratory and expiratory V(T), airway pressure, end-tidal CO(2) partial pressure, and pulse oximetry were recorded. The leak fraction was calculated as the difference between the inspiratory and expiratory V(T) divided by the inspiratory V(T). Postoperative sore throat frequency was scored in the recovery room ("early") and 1 week after surgery ("late"). MAIN RESULTS: All patients were successfully ventilated through the assigned laryngeal mask. The leak fraction was 7 +/- 3% with the LMA and 7 +/- 4% with the PLMA (p = 0.731). In one patient, the PLMA drainage tube was not patent despite a leak fraction of 5%, and there was no clinically detectable air leak. During the recovery room stay, the frequency of sore throat was scored as mild in 13% and 10% of patients with the standard LMA and the PLMA, respectively, and was absent in the remaining patients (p = 0.99, between groups). There were no differences in the frequency of sore throat between the "early" and "late" evaluations (p = 0.99). CONCLUSIONS: The PLMA and the LMA show similar airtight efficiency during laparoscopy. The patency of the PLMA drainage tube should always be confirmed. The sore throat evaluation performed in recovery room appears as reliable as later evaluations.