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2.
Case Rep Obstet Gynecol ; 2014: 928079, 2014.
Article in English | MEDLINE | ID: mdl-25506009

ABSTRACT

Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome associated with a number of conditions including preeclampsia. It is characterized by seizures, alteration of consciousness, visual disturbances, and symmetric white matter abnormalities, typically in the posterior parietooccipital regions of the cerebral hemispheres, at computed tomography (CT) and magnetic resonance (MRI). We report three new cases of PRES in preeclamptic patients and describe the management of these patients. We present a brief review of other cases in the literature, with particular attention to the anesthetic management.

3.
Minerva Anestesiol ; 79(10): 1147-55, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24002458

ABSTRACT

BACKGROUND: Thanks to significant technical improvements, VA-ECMO is increasingly used to reverse circulatory collapse refractory to standard treatments. METHODS: We studied patients who underwent VA-ECMO due to primary cardiogenic shock or cardiac arrest between January 2008 and June 2011 at our institution. Variables related to hospital survival were analyzed. Long-term survival and health-related quality of life were checked. RESULTS: VA-ECMO was instituted in 23 patients: 17 outpatients and 6 inpatients. Seven of the outpatients were admitted to hospital under ongoing CPR. In these pts, time to CPR was 7 min (6-8) and time to ECMO 93 min (74-107); after 20 hours (16-22), all these pts died. Among remaining 16 pts, 6 were bridged to heart transplant and 4 to heart recovery, 8 survived to hospital discharge and 7 were alive with high health-related quality of life after 46 months (36-54). Ongoing CPR, inotropic score and lactates at cannulation did not differ between survivors and non-survivors; duration of shock, SOFA score and serum creatinine at ECMO institution, and lactates and fluid balance after 36 hours were higher in non-survivors. Patients could be kept on spontaneous breathing for >30% of time while on VA-ECMO. CONCLUSION: Emergency VA-ECMO institution can reverse refractory acute cardiovascular collapse, provided it is carried out before significant organ dysfunction occurs. Light sedation and spontaneous breathing while on VA-ECMO can be well tolerated by patients, but related clinical benefits should be proved. Patients successfully bridged to heart recovery or transplant are candidates for long-term good quality of life.


Subject(s)
Extracorporeal Membrane Oxygenation , Hospital Mortality , Quality of Life , Shock/mortality , Shock/therapy , Survival , Survivors/psychology , Adult , Cardiopulmonary Resuscitation , Emergency Medical Services , Female , Heart Arrest/mortality , Heart Arrest/psychology , Heart Arrest/therapy , Humans , Male , Middle Aged , Shock/psychology , Shock, Cardiogenic/mortality , Shock, Cardiogenic/psychology , Shock, Cardiogenic/therapy , Treatment Outcome , Ventilator Weaning
4.
Minerva Anestesiol ; 78(2): 168-75, 2012 02.
Article in English | MEDLINE | ID: mdl-21750485

ABSTRACT

BACKGROUND: Surgery of spontaneous supratentorial intracerebral hemorrhage (ICH), especially if performed early, can be complicated by rebleeding, a condition that can worsen the outcome. We evaluated the effect of recombinant activated factor VII (rFVIIa) on postoperative rebleeding. METHODS: In this randomized, open-label, single-blinded study, 21 patients with spontaneous supratentorial ICH diagnosed by computed tomography (CT) scan were treated with intravenous rFVIIa (100 mcg/Kg b.w., N=13) or placebo (N=8). Hematoma volume was assessed using CT scan immediately, 18-30 hours, and 5-7 days after hematoma evacuation. The primary endpoint was a hematoma volume at 18-30 hours after surgery. All CT scans were evaluated at one center by the same investigator who was unaware of the treatment. Hematoma volume was measured using dedicated software. RESULTS: At baseline, the hematoma volume was 59.2±27.4 and 71.5±32.1 mL in the rFVIIa and placebo group, respectively. Hematoma evacuation resulted in significantly smaller ICH volumes that were similar in the rFVIIa and placebo group at 18-30 hours after surgery (15.9±14.2 mL and 18±15.1 mL, respectively; mean difference 2.1 mL, 95% confidence interval -12.1 to 16.2, P=0.76 (0.03 mL after adjustment for baseline value)). The frequencies of deep venous thrombosis, myocardial infarction, troponin I elevation and cerebral ischemia were similar in both groups. CONCLUSION: In this pilot study, intraoperative, intravenous rFVIIa administration did not modify hematoma volume after early ICH surgery. However, the 95% CI was wide, which indicates considerable uncertainty. Therefore, our results do not disprove the potential benefit of rFVIIa administration, which could be shown in a larger study.


Subject(s)
Cerebral Hemorrhage/surgery , Factor VIIa/administration & dosage , Hematoma/pathology , Hematoma/prevention & control , Intraoperative Care , Postoperative Complications/pathology , Postoperative Complications/prevention & control , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Prospective Studies , Recombinant Proteins/administration & dosage , Single-Blind Method , Time Factors
5.
Minerva Anestesiol ; 76(7): 500-3, 2010 07.
Article in English | MEDLINE | ID: mdl-20613690

ABSTRACT

AIM: An increased thyroxine requirement has been described in hypothyroid patients who have chronic gastritis as well as in patients who are treated with drugs that modify the acidic environment of the stomach. Patients with acute critical illnesses are generally treated with calorically dense enteral solutions and antacids, both of which influence the gastric acidic environment. In this study, we evaluated levothyroxine (L-thyroxine) requirements in hypothyroid patients admitted to our ICU. METHODS: The medical records of nine patients with pre-existing hypothyroidism who did not have gastrointestinal diseases and who were admitted to our ICU between 2003 and 2008 were retrospectively reviewed. Serum TSH, FT4, and FT3 levels were measured at the time of admission and every four to eight days thereafter. After the second measurement of these parameters, patients' L-thyroxine doses were adjusted to maintain their TSH concentrations at baseline levels. RESULTS: At the time of ICU admission, the median [interquartile range] TSH, FT4, and FT3 values of the included patients were 1.52 [0.79-3.8] mU/L, 6.5 [4.9-9.3] pg/mL, and 1.0 [<1.0-1.25] pg/mL, respectively. After the first 4-8 days of their ICU stay, while their L-thyroxine doses were unchanged, the TSH levels of all included patients increased (5.69 [3.87-6.83] mU/L, P=0.012). Over the same period, their FT4 levels decreased significantly. To restore patients' TSH levels to those at the time of admission, the L-thyroxine dose was increased in 8/9 patients by an average of 54.4+/-31.6% (P=0.001). At the time of ICU discharge, patients' TSH and FT4 levels had returned to near their levels at the time of admission. All patients' serum FT3 levels remained low throughout the entire duration of their ICU stay. CONCLUSION: To maintain TSH levels in the normal range, it may be necessary to increase the L-thyroxine dose of critically ill patients with hypothyroidism. Our findings also suggest that during the first several days of a critical illness, the hypothalamic-pituitary-thyroid axis is not suppressed in hypothyroid patients.


Subject(s)
Hypothyroidism/drug therapy , Thyroxine/therapeutic use , Adult , Aged , Aged, 80 and over , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies , Thyroxine/administration & dosage
6.
Int J Artif Organs ; 27(8): 709-16, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15478542

ABSTRACT

OBJECTIVE: Evaluation of the respiratory pattern selected by the Adaptive Support Ventilation (ASV) in ventilated patients with acute, chronic respiratory failure and normal lungs and in a physical lung model. DESIGN: We tested ASV both on patients and in a physical lung model, with a normal level of minute ventilation and with minute ventilation increased by 30%. In each patient, respiratory pattern, mechanics and blood gases were recorded. SETTING: General ICU of a University Hospital. RESULTS: In patients with normal lungs, mean values+/-SD were: tidal volume (Vt) 558.1+/-142.4 mL, respiratory rate (RR) 12.6+/-1.3b/min and inspiratory time/total time ratio (Ti/Ttot) 42.4+/-4.1%; in COPD, mean values+/-SD were: Vt 724+/-171 mL, RR 9.2+/-2.7b/min and Ti/Ttot 26.6+/-10.5%; in restrictive ones, mean values+/-SD were: Vt 550.2+/-77.0 mL, RR 15.8+/-2.6b/min, Ti/Ttot 47.5+/-2.5%. In the lung model, at a normal setting, mean values+/-SD were: Vt 523+/-18.5 mL, RR 14+/-0.0b/min, Ti/Ttot 44.0%, in COPD, mean values+/-SD were: Vt 678+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.7%, in restrictive one, mean values+/-SD were: Vt 513+/-12.8 mL, RR 15+/-0.0b/min, Ti/Ttot 48+/-1.5%. In model hyperventilation conditions in a normal setting a Vt of 582+/-16.6 mL, RR 16+/-0.0b/min, Ti/Ttot 48+/-0.0% were selected, in the obstructive setting Vt 883+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.0% and in a restrictive one Vt 545+/-8.4 mL, RR 18+/-0.0b/min, Ti/Ttot 50-0.0%. CONCLUSIONS: In normal patients ASV selected a ventilatory pattern close to the physiological one, in COPD almost a high expiratory time pattern and in restrictive ones a reduced tidal volume pattern. In the model the selection was similar. In the hyperventilation test, ASV chose a balanced increase in both Vt and RR.


Subject(s)
Models, Biological , Paralysis/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiration, Artificial/methods , Respiratory Distress Syndrome/physiopathology , Carbon Dioxide/blood , Female , Humans , Hydrogen-Ion Concentration , Hyperventilation/physiopathology , Inspiratory Capacity/physiology , Male , Middle Aged , Monitoring, Physiologic , Oxygen/blood , Pulmonary Disease, Chronic Obstructive/therapy , Reference Values , Respiration , Respiratory Distress Syndrome/therapy
7.
Minerva Anestesiol ; 68(5): 365-8, 2002 May.
Article in English | MEDLINE | ID: mdl-12029247

ABSTRACT

Adaptive Support Ventilation is a novel ventilation mode, a closed-loop control mode that may switch automatically from a PCV-like behaviour to an SIMV-like or PSV-like behaviour, according to the patient status. The operating principles are based on pressure-controlled SIMV with pressure levels and SIMV rate automatically adjusted according to measured lung mechanics at each breath. ASV provided a safe and effective ventilation in patients with normal lungs, restrective or obstructive diseases. In cardiac surgery tracheal extrubation was faster in ASV patients then in controls. In the early weaning phase of acute ventilatory insufficiency the need of resetting ventilator parameters was decreased, suggesting potential benefit for patient care.


Subject(s)
Respiration, Artificial/methods , Critical Care , Humans , Intraoperative Period , Respiration, Artificial/instrumentation , Ventilators, Mechanical
9.
Respir Care Clin N Am ; 7(3): 441-64, ix, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11517033

ABSTRACT

Conventional mechanical ventilation modes fail to provide a setting for direct control of a patient's ventilatory effort; however, with all modes clinicians may manipulate conventional controls to modulate the spontaneous respiratory activity of the patient. For instance, during pressure support ventilation the spontaneous respiratory activity can be decreased by increasing the pressure support level to achieve an adequate residual load for the respiratory muscles of the patient, neither too high nor too low. This choice is based on the clinical observation. A closed-loop controller can be envisaged to accomplish automatically, precisely, and on a breath-by-breath basis, this difficult task. The closed-loop controller should be based on the continuous and possibly noninvasive monitoring of a parameter that quantitatively reflects the patient's effort for ventilation. Occlusion pressure at 0.1 second (P0.1) can be the ideal parameter for that purpose. The authors have designed a noninvasive method for breath-by-breath monitoring of P0.1, and then a closed-loop control mode that automatically adapts the pressure support level to reach and maintain a user-set P0.1 and alveolar volume. This article discusses features and performance of this P0.1 control mode, fields of application, known limits, and possible future improvements.


Subject(s)
Feedback , Respiration, Artificial , Algorithms , Humans , Monitoring, Physiologic/methods , Respiratory Mechanics , Work of Breathing
10.
Crit Care ; 3(5): R77-82, 1999.
Article in English | MEDLINE | ID: mdl-11094485

ABSTRACT

Although they represent a valuable alternative to heated humidifiers, artificial noses have unfavourable mechanical effects. Most important of these is the increase in dead space, with consequent increase in the ventilation requirement. Also, artificial noses increase the inspiratory and expiratory resistance of the apparatus, and may mildly increase intrinsic positive end-expiratory pressure. The significance of these effects depends on the design and function of the artificial nose. The pure humidifying function results in just a moderate increase in dead space and resistance of the apparatus, whereas the combination of a filtering function with the humidifying function may critically increase the volume and the resistance of the artificial nose, especially when a mechanical filter is used. The increase in the inspiratory load of ventilation that is imposed by artificial noses, which is particularly significant for the combined heat-moisture exchanger filters, should be compensated for by an increase either in ventilator output or in patient's work of breathing. Although both approaches can be tolerated by most patients, some exceptions should be considered. The increased pressure and volume that are required to compensate for the artificial nose application increase the risk of barotrauma and volutrauma in those patients who have the most severe alterations in respiratory mechanics. Moreover, those patients who have very limited respiratory reserve may not be able to compensate for the inspiratory work imposed by an artificial nose. When we choose an artificial nose, we should take into account the volume and resistance of the available devices. We should also consider the mechanical effects of the artificial noses when setting mechanical ventilation and when assessing a patient's ability to breathe spontaneously.


Subject(s)
Respiration, Artificial/instrumentation , Filtration , Humans , Humidity , Positive-Pressure Respiration, Intrinsic , Respiration, Artificial/adverse effects , Respiratory Mechanics , Work of Breathing
11.
Eur Respir J ; 12(5): 1164-71, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9864015

ABSTRACT

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.


Subject(s)
Nitric Oxide/administration & dosage , Respiratory Distress Syndrome/physiopathology , Administration, Inhalation , Adolescent , Adult , Aged , Dose-Response Relationship, Drug , Female , Hemodynamics/drug effects , Humans , Male , Middle Aged , Pulmonary Circulation/drug effects , Pulmonary Gas Exchange/drug effects , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Respiratory Mechanics/drug effects
12.
Intensive Care Med ; 23(4): 399-405, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9142578

ABSTRACT

OBJECTIVE: To investigate the mechanical effects of artificial noses. SETTING: A general intensive care unit of a university hospital. PATIENTS: 10 patients in pressure support ventilation for acute respiratory failure. INTERVENTIONS: The following three conditions were randomly tested on each patient: the use of a heated humidifier (control condition), the use of a heat and moisture exchanger without filtering function (HME), and the use of a combined heat and moisture exchanger and mechanical filter (HMEF). The pressure support level was automatically adapted by means of a closed-loop control in order to obtain constancy, throughout the study, of patient inspiratory effort as evaluated from airway occlusion pressure at 0.1 s (P0.1). Patient's ventilatory pattern, P0.1, work of breathing, and blood gases were recorded. MEASUREMENTS AND MAIN RESULTS: The artificial noses increased different components of the inspiratory load: inspiratory resistance, ventilation requirements (due to increased dead space ventilation), and dynamic intrinsic positive end-expiratory pressure (PEEP). The additional load imposed by the artificial noses was entirely undertaken by the ventilator, being the closed-loop control of P0.1 effective to maintain constancy of patient inspiratory work by means of adequate increases in pressure support level. CONCLUSIONS: The artificial noses cause unfavorable mechanical effects by increasing inspiratory resistance, ventilation requirements, and dynamic intrinsic PEEP. Clinicians should consider these effects when setting mechanical ventilation and when assessing patients' ability to breathe spontaneously.


Subject(s)
Artificial Organs/adverse effects , Critical Care/methods , Nose , Respiration, Artificial/methods , Adult , Aged , Aged, 80 and over , Cross-Over Studies , Female , Filtration/instrumentation , Hot Temperature , Humans , Humidity , Longitudinal Studies , Male , Middle Aged , Positive-Pressure Respiration, Intrinsic/etiology
13.
Crit Care Med ; 24(5): 771-9, 1996 May.
Article in English | MEDLINE | ID: mdl-8706452

ABSTRACT

OBJECTIVE: Airway occlusion pressure at 0.1 sec (P0.1) is an index of respiratory center output. During pressure-support ventilation, P0.1 correlates with the mechanical output of the inspiratory muscles and has an inverse relationship with the amount of pressure-support ventilation. Based on these observations, we designed a closed-loop control which, by automatically adjusting pressure-support ventilation, stabilizes P0.1, and hence patient inspiratory activity, at a desired target. The purpose of the study was to demonstrate the feasibility of the method, rather than its efficacy or even its influence on patient outcome. DESIGN: Prospective, randomized trial. SETTING: A general intensive care unit of a university hospital in Italy. PATIENTS: Eight stable patients intubated and ventilated with pressure-support ventilation for acute respiratory failure. INTERVENTIONS: Patients were transiently connected to a computer-controlled ventilator on which the algorithm for closed-loop control was implemented. The closed-loop control was based on breath by breath measurement of P0.1, and on comparison with a target set by the user. When actual P0.1 proved to be higher than the target value, the P0.1 controller automatically increased pressure-support ventilation, and decreased it when P0.1 proved to be lower than the target value. For safety, a volume controller was also implemented. Four P0.1 targets (1.5, 2.5, 3.5, and 4.5 cm H2O) were applied at random for 15 mins each. MEASUREMENTS AND MAIN RESULTS: The closed-loop algorithm was able to control P0.1, with a difference from the set targets of 0.59 +/- 0.27 (SD) cm H2O. CONCLUSIONS: The study shows that P0.1 can be automatically controlled by pressure-support ventilation adjustments with a computer. Inspiratory activity can thus be stabilized at a level prescribed by the physician.


Subject(s)
Airway Resistance , Feedback , Positive-Pressure Respiration/methods , Respiratory Insufficiency/therapy , Therapy, Computer-Assisted/methods , Acute Disease , Adult , Aged , Aged, 80 and over , Airway Resistance/physiology , Algorithms , Feasibility Studies , Female , Humans , Intubation, Intratracheal , Male , Middle Aged , Pressure , Prospective Studies , Respiratory Insufficiency/physiopathology , Treatment Outcome , Work of Breathing
14.
Chest ; 108(1): 208-15, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7606960

ABSTRACT

OBJECTIVE: The measurement of esophageal pressure (Pes) is the conventional method for the evaluation of the forces applied to the respiratory system by the respiratory muscles. As an alternative to Pes measurement, we propose the calculation of the instantaneous net pressure applied by the respiratory muscles [Pmusc(t)]. DESIGN: Prospective, randomized study. SETTING: A general ICU of a university hospital. PATIENTS: Eight intubated patients submitted to pressure support ventilation for acute respiratory failure. INTERVENTIONS: Four different levels of pressure support were used to unload progressively the respiratory muscles. Pmusc(t) was calculated at all levels of pressure support and compared with Pes corrected for chest wall load as a reference. Pmusc(t) was further used to calculate inspiratory work of breathing, which in turn was compared with data obtained with the conventional method. MEASUREMENTS AND RESULTS: Airway pressure, airflow, and Pes were measured. Both for amplitude and for timing, Pmusc(t) showed good agreement with reference measurements. Work of breathing as calculated from Pmusc(t) agreed well with the measurement obtained with the conventional method (mean difference, 0.057 +/- 0.157 J). CONCLUSIONS: Noninvasive evaluation of Pmusc(t) allows extended monitoring of mechanical ventilation, which is particularly interesting for pressure preset ventilation modes.


Subject(s)
Respiration, Artificial , Respiratory Insufficiency/physiopathology , Respiratory Mechanics , Respiratory Muscles/physiopathology , Adult , Aged , Biomechanical Phenomena , Female , Humans , Male , Middle Aged , Monitoring, Physiologic , Prospective Studies , Respiratory Insufficiency/therapy , Work of Breathing
15.
Intensive Care Med ; 21(5): 406-13, 1995 May.
Article in English | MEDLINE | ID: mdl-7665750

ABSTRACT

OBJECTIVE: To evaluate a least squares fitting technique for the purpose of measuring total respiratory compliance (Crs) and resistance (Rrs) in patients submitted to partial ventilatory support, without the need for esophageal pressure measurement. DESIGN: Prospective, randomized study. SETTING: A general ICU of a University Hospital. PATIENTS: 11 patients in acute respiratory failure, intubated and assisted by pressure support ventilation (PSV). INTERVENTIONS: Patients were ventilated at 4 different levels of pressure support. At the end of the study, they were paralyzed for diagnostic reasons and submitted to volume controlled ventilation (CMV). MEASUREMENTS AND RESULTS: A least squares fitting (LSF) method was applied to measure Crs and Rrs at different levels of pressure support as well as in CMV. Crs and Rrs calculated by the LSF method were compared to reference values which were obtained in PSV by measurement of esophageal pressure, and in CMV by the application of the constant flow, end-inspiratory occlusion method. Inspiratory activity was measured by P0.1. In CMV, Crs and Rrs measured by the LSF method are close to quasistatic compliance (-1.5 +/- 1.5 ml/cmH2O) and to the mean value of minimum and maximum end-inspiratory resistance (+0.9 +/- 2.5 cmH2O/(l/s)). Applied during PSV, the LSF method leads to gross underestimation of Rrs (-10.4 +/- 2.3 cmH2O/(l/s)) and overestimation of Crs (+35.2 +/- 33 ml/cmH2O) whenever the set pressure support level is low and the activity of the respiratory muscles is high (P0.1 was 4.6 +/- 3.1 cmH2O). However, satisfactory estimations of Crs and Rrs by the LSF method were obtained at increased pressure support levels, resulting in a mean error of -0.4 +/- 6 ml/cmH2O and -2.8 +/- 1.5 cmH2O/(l/s), respectively. This condition was coincident with a P0.1 of 1.6 +/- 0.7 cmH2O. CONCLUSION: The LSF method allows non-invasive evaluation of respiratory mechanics during PSV, provided that a near-relaxation condition is obtained by means of an adequately increased pressure support level. The measurement of P0.1 may be helpful for titrating the pressure support in order to obtain the condition of near-relaxation.


Subject(s)
Airway Resistance , Lung Compliance , Pancuronium/therapeutic use , Positive-Pressure Respiration/methods , Respiratory Insufficiency/therapy , Acute Disease , Adult , Aged , Airway Resistance/drug effects , Female , Humans , Least-Squares Analysis , Lung Compliance/drug effects , Male , Middle Aged , Monitoring, Physiologic/methods , Prospective Studies , Reproducibility of Results , Respiratory Insufficiency/physiopathology
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