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Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):231-236
DOI 10.1590/S0103-507X2009000300001
OBJECTIVE: This study aimed to analyze outcome, clinical and epidemiological characteristics and severity factors in adult patients admitted with a diagnosis of infection by virus A (H1N1) to public and private intensive care units, in Paraná, Brazil. METHODS: Cohort study of medical charts of patients older than 12 years admitted to 11 intensive care units in 6 cities in the state of Parana, Brazil, during a period of 45 days, with diagnosis of swine influenza. The diagnosis of infection with A (H1N1) was made by real time polymerase chain reaction (RT-PCR) of nasopharyngeal secretion, or strong clinical suspicion when other causes had been ruled out (even with negative RT-PCR). Descriptive statistics were performed, analysis by the Chi square test was used to compare percentages and the Student's t test for continuous variables with univariate analysis, assuming a significance level of p <0.05. RESULTS: There were 63 adult patients admitted with a diagnosis of H1N1, 37 (58.7%) being RT-PCR positive. Most patients were young adults (65% under 40 years of age) with no gender predominance and high incidence of obesity (27.0% with Body Mass Index > 30). Mean of the Acute Physiologic Chronic Health Evaluation II (APACHE II) score was 15.0 + 8.1. Mortality in the intensive care unit was 39.7%. The main factors associated with mortality were: positive RT-PCR, low levels of initial PaO2/FiO2, high initial levels of urea and lactate dehydrogenase, required level of positive end expiratory pressure, need for the prone position and vasopressors. CONCLUSIONS: Adult patients with A (H1N1) virus infection admitted to intensive care units had a high risk of death, particularly due to respiratory impairment. Positive RT-PCR, urea and lactic dehydrogenase, low initial PaO2/FiO2 and high levels of PEEP were correlated with higher mortality.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):231-236
DOI 10.1590/S0103-507X2009000300001
OBJECTIVE: This study aimed to analyze outcome, clinical and epidemiological characteristics and severity factors in adult patients admitted with a diagnosis of infection by virus A (H1N1) to public and private intensive care units, in Paraná, Brazil. METHODS: Cohort study of medical charts of patients older than 12 years admitted to 11 intensive care units in 6 cities in the state of Parana, Brazil, during a period of 45 days, with diagnosis of swine influenza. The diagnosis of infection with A (H1N1) was made by real time polymerase chain reaction (RT-PCR) of nasopharyngeal secretion, or strong clinical suspicion when other causes had been ruled out (even with negative RT-PCR). Descriptive statistics were performed, analysis by the Chi square test was used to compare percentages and the Student's t test for continuous variables with univariate analysis, assuming a significance level of p <0.05. RESULTS: There were 63 adult patients admitted with a diagnosis of H1N1, 37 (58.7%) being RT-PCR positive. Most patients were young adults (65% under 40 years of age) with no gender predominance and high incidence of obesity (27.0% with Body Mass Index > 30). Mean of the Acute Physiologic Chronic Health Evaluation II (APACHE II) score was 15.0 + 8.1. Mortality in the intensive care unit was 39.7%. The main factors associated with mortality were: positive RT-PCR, low levels of initial PaO2/FiO2, high initial levels of urea and lactate dehydrogenase, required level of positive end expiratory pressure, need for the prone position and vasopressors. CONCLUSIONS: Adult patients with A (H1N1) virus infection admitted to intensive care units had a high risk of death, particularly due to respiratory impairment. Positive RT-PCR, urea and lactic dehydrogenase, low initial PaO2/FiO2 and high levels of PEEP were correlated with higher mortality.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):237-246
DOI 10.1590/S0103-507X2009000300002
INTRODUCTION: The clinical profile as well as the therapeutic and diagnostic strategies for patients with pulmonary embolism, describes clinical practice in the approach of the disease. Such information, scarce in national studies, enables a better understanding of pulmonary embolism. METHODS: A multicenter trial included 727 patients with pulmonary embolism who were admitted in emergency or intensive care unit. Diagnostic criteria for inclusion were: 1. Visibility of thrombus in the pulmonary artery at pulmonary arteriography, helical computer tomography, magnetic resonance or echocardiogram. 2. High probability at pulmonary scintigraphy. 3. Venous duplex-scan with thrombus and clinical manifestations of pulmonary embolism. Clinical and complementary exams were analyzed. RESULTS: Mean age was 68 years, 42% were male. Most prevalent risk factors were: age>40 years, bed rest and neoplasm. More frequent signs and symptoms were: dyspnea, tachypnea, sinus tachycardia, and chest pain. Changes were observed at electrocardiogram in 30%, at chest X-ray in 45%, at venous duplex-scan in 67%, at transthoracic echocardiogram in 37%. . D-dimer, troponin I and CKMB were positive in, respectively, 93, 9 and 8%. Most frequently used methods to confirm diagnosis were helical computer tomography and non-fractioned heparin was the treatment most used. In-hospital mortality was 19.5%. CONCLUSIONS: It was observed that age>40 years, prolonged rest and neoplasms were the most prevalent risk factors and dyspnea and tachypnea were the more frequent clinical manifestations. Helical computer tomography was the most often used method to confirm diagnosis and non-fractioned heparin was the main form of treatment.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):237-246
DOI 10.1590/S0103-507X2009000300002
INTRODUCTION: The clinical profile as well as the therapeutic and diagnostic strategies for patients with pulmonary embolism, describes clinical practice in the approach of the disease. Such information, scarce in national studies, enables a better understanding of pulmonary embolism. METHODS: A multicenter trial included 727 patients with pulmonary embolism who were admitted in emergency or intensive care unit. Diagnostic criteria for inclusion were: 1. Visibility of thrombus in the pulmonary artery at pulmonary arteriography, helical computer tomography, magnetic resonance or echocardiogram. 2. High probability at pulmonary scintigraphy. 3. Venous duplex-scan with thrombus and clinical manifestations of pulmonary embolism. Clinical and complementary exams were analyzed. RESULTS: Mean age was 68 years, 42% were male. Most prevalent risk factors were: age>40 years, bed rest and neoplasm. More frequent signs and symptoms were: dyspnea, tachypnea, sinus tachycardia, and chest pain. Changes were observed at electrocardiogram in 30%, at chest X-ray in 45%, at venous duplex-scan in 67%, at transthoracic echocardiogram in 37%. . D-dimer, troponin I and CKMB were positive in, respectively, 93, 9 and 8%. Most frequently used methods to confirm diagnosis were helical computer tomography and non-fractioned heparin was the treatment most used. In-hospital mortality was 19.5%. CONCLUSIONS: It was observed that age>40 years, prolonged rest and neoplasms were the most prevalent risk factors and dyspnea and tachypnea were the more frequent clinical manifestations. Helical computer tomography was the most often used method to confirm diagnosis and non-fractioned heparin was the main form of treatment.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):247-254
DOI 10.1590/S0103-507X2009000300003
OBJECTIVES: Availability of state-of-the-art technology at intensive care units has often turned into a tool aggravating suffering by prolonging the end-of-life process. Distinguishing therapeutic persistence from therapeutic obstinacy has become a great challenge for present-day medicine. The aim of this study was to assess the benefit-harm relation in the use of life-sustaining therapies by means of an evolutionary system of individual prognostic assessment. METHODS: A cohort, prospective, observational study at the intensive care unit of the São Francisco De Paula University Hospital of UCPel, Pelotas RS from March 2006 to August 31, 2007. Individual prognostic assessments were recorded by using an evolutionary system, the UNICAMP II index, associated with albumin transferrin and lymphocytes serum levels, life- sustaining therapies and the outcome. Statistical analysis was carried out by the Student's t-test, ANOVA test, Chi-square test, Fisher's exact test, Spearman's correlation test and area under the receiver-operating characteristic curve. A p value < 0.05 was considered statistically significant. RESULTS: Four hundred forty seven patients were assessed during the study. Prevalence of death was significantly higher among those who received life-sustaining therapies at a later stage of the intervention, and those whose prognostic index and nutritional status worsened at an early stage of intervention. CONCLUSION: Assessment of individual evolutionary prognostic proved to be a useful method to objectively subsidize ethical decisions related to therapeutic persistence and therapeutic obstinacy.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):247-254
DOI 10.1590/S0103-507X2009000300003
OBJECTIVES: Availability of state-of-the-art technology at intensive care units has often turned into a tool aggravating suffering by prolonging the end-of-life process. Distinguishing therapeutic persistence from therapeutic obstinacy has become a great challenge for present-day medicine. The aim of this study was to assess the benefit-harm relation in the use of life-sustaining therapies by means of an evolutionary system of individual prognostic assessment. METHODS: A cohort, prospective, observational study at the intensive care unit of the São Francisco De Paula University Hospital of UCPel, Pelotas RS from March 2006 to August 31, 2007. Individual prognostic assessments were recorded by using an evolutionary system, the UNICAMP II index, associated with albumin transferrin and lymphocytes serum levels, life- sustaining therapies and the outcome. Statistical analysis was carried out by the Student's t-test, ANOVA test, Chi-square test, Fisher's exact test, Spearman's correlation test and area under the receiver-operating characteristic curve. A p value < 0.05 was considered statistically significant. RESULTS: Four hundred forty seven patients were assessed during the study. Prevalence of death was significantly higher among those who received life-sustaining therapies at a later stage of the intervention, and those whose prognostic index and nutritional status worsened at an early stage of intervention. CONCLUSION: Assessment of individual evolutionary prognostic proved to be a useful method to objectively subsidize ethical decisions related to therapeutic persistence and therapeutic obstinacy.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):255-261
DOI 10.1590/S0103-507X2009000300004
Currently, aging of the population is a widespread global phenomenon. Therefore, the assessment of prognosis in elderly patients is needed. This study aims to identify risk factors in a population of elderly patients admitted in the intensive care unit METHODS: A prospective study in the intensive care unit of a general tertiary hospital was carried out for five months. Patients with 65 years or more of age, who stayed in the intensive care unit for 24 hours or more were included and those at the-end-of-life, patients readmitted to intensive care unit during the same hospital stay were excluded. RESULTS: In this study 199 patients were involved, with a mean age of 75.4±6.8 years, and 58.8% were female. Mortality was 57.3%. The mean APACHE II, SOFA, MODS and Katz index (assessment of daily activities) were respectively 20.0±5.8, 6.8±3.9, 2.4±1.9 and 5.3±1.6. Most patients were postoperative 59.3% and 41.6% were under invasive mechanical ventilation. At regression analysis, the independent determinants of higher mortality were: older age (76.9±6.7 years death versus 73.3±6.5 years discharge, P<0.001, OR=1.08, CI 95% 1.01-1. 16), the Katz index (4.9±1.9 deaths versus 5.7±0.9 discharge, p=0.001, OR=0.66, CI 95% 0.45-0.98), hyperglycemia (158.1±69.0 death versus 139.6±48.5 discharge p=0.041; OR=1.02; CI 95% 1.01-1.03) and need for mechanical ventilation at admission to the intensive care unit (57.0% death versus 20.5% discharge p <0.001, OR=3.57, CI 95% 1.24-10.3). CONCLUSION: Elderly patients admitted to the intensive care unit that have difficulties in performing daily activities, hyperglycemia and who are under invasive mechanical ventilation had a worse hospital prognosis.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):255-261
DOI 10.1590/S0103-507X2009000300004
Currently, aging of the population is a widespread global phenomenon. Therefore, the assessment of prognosis in elderly patients is needed. This study aims to identify risk factors in a population of elderly patients admitted in the intensive care unit METHODS: A prospective study in the intensive care unit of a general tertiary hospital was carried out for five months. Patients with 65 years or more of age, who stayed in the intensive care unit for 24 hours or more were included and those at the-end-of-life, patients readmitted to intensive care unit during the same hospital stay were excluded. RESULTS: In this study 199 patients were involved, with a mean age of 75.4±6.8 years, and 58.8% were female. Mortality was 57.3%. The mean APACHE II, SOFA, MODS and Katz index (assessment of daily activities) were respectively 20.0±5.8, 6.8±3.9, 2.4±1.9 and 5.3±1.6. Most patients were postoperative 59.3% and 41.6% were under invasive mechanical ventilation. At regression analysis, the independent determinants of higher mortality were: older age (76.9±6.7 years death versus 73.3±6.5 years discharge, P<0.001, OR=1.08, CI 95% 1.01-1. 16), the Katz index (4.9±1.9 deaths versus 5.7±0.9 discharge, p=0.001, OR=0.66, CI 95% 0.45-0.98), hyperglycemia (158.1±69.0 death versus 139.6±48.5 discharge p=0.041; OR=1.02; CI 95% 1.01-1.03) and need for mechanical ventilation at admission to the intensive care unit (57.0% death versus 20.5% discharge p <0.001, OR=3.57, CI 95% 1.24-10.3). CONCLUSION: Elderly patients admitted to the intensive care unit that have difficulties in performing daily activities, hyperglycemia and who are under invasive mechanical ventilation had a worse hospital prognosis.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):262-268
DOI 10.1590/S0103-507X2009000300005
OBJECTIVES: To describe the population of aged as compared to young patients under mechanical ventilation and to analyze the mortality risk factors of this group in an intensive care unit. METHODS: This was a prospective observational trial in patients over 18 years of age, admitted in an intensive care unit and under mechanical ventilation, during one year. Patients were divided into two groups according to age: Group 1 - patients over 65 years old; and Group 2, 65 years old or younger. RESULTS: eighty one mechanic ventilation patients were included, 62 aged and 18 younger, mean ages from aged was 76 years, while in the younger it was 56 years. As compared to the control, aged patients had longer mechanic ventilation time , higher intensive care unit and hospital mortality: 63.1% versus 26.3% and 74.2% versus 47.4% (P<0.05), respectively. In addition, the aged under mechanic ventilation had increased desintubation failures, difficult ventilatory weaning and deaths directly related to respiratory dysfunction. The mechanic ventilation time was an independent risk factor for death in the intensive care unit in aged patients (OR= 2.7, p=0.02). The area under the ROC curve of mechanic ventilation about intensive care unit death was 0.92 (95% CI 0.85-0.97, p (area 0.5)=0.0001), cutoff point of 4 days, sensitivity 89.4% and specificity 77.1%. CONCLUSIONS: Mechanic ventilation patients over 65years of age have a worse prognosis than the younger, and the longer the mechanic ventilation time, the higher will be intensive care mortality.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):262-268
DOI 10.1590/S0103-507X2009000300005
OBJECTIVES: To describe the population of aged as compared to young patients under mechanical ventilation and to analyze the mortality risk factors of this group in an intensive care unit. METHODS: This was a prospective observational trial in patients over 18 years of age, admitted in an intensive care unit and under mechanical ventilation, during one year. Patients were divided into two groups according to age: Group 1 - patients over 65 years old; and Group 2, 65 years old or younger. RESULTS: eighty one mechanic ventilation patients were included, 62 aged and 18 younger, mean ages from aged was 76 years, while in the younger it was 56 years. As compared to the control, aged patients had longer mechanic ventilation time , higher intensive care unit and hospital mortality: 63.1% versus 26.3% and 74.2% versus 47.4% (P<0.05), respectively. In addition, the aged under mechanic ventilation had increased desintubation failures, difficult ventilatory weaning and deaths directly related to respiratory dysfunction. The mechanic ventilation time was an independent risk factor for death in the intensive care unit in aged patients (OR= 2.7, p=0.02). The area under the ROC curve of mechanic ventilation about intensive care unit death was 0.92 (95% CI 0.85-0.97, p (area 0.5)=0.0001), cutoff point of 4 days, sensitivity 89.4% and specificity 77.1%. CONCLUSIONS: Mechanic ventilation patients over 65years of age have a worse prognosis than the younger, and the longer the mechanic ventilation time, the higher will be intensive care mortality.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):276-282
DOI 10.1590/S0103-507X2009000300007
OBJECTIVE: The understanding of adverse events may simplify the inquiry regarding the quality of nursing care, presuming a foregrounding role in evaluating health services. The aim of the study was to identify adverse events in nursing care in an intensive care unit. METHODS: Data were collected using an appropriate form known as problem-oriented record (POR) over a 10-month period; patients were monitored throughout their intensive care unit stay. RESULTS: Over the study period, 550 adverse events were recorded as follows: 26 concerned the "five rights" related to drug administration; 23 to non-administered medication; 181 to inappropriate medication records; 28 to failure in infusion pump assembly; 17 to not performed inhalation; 8 to incorrect handling of needles and syringes; 53 to not performed nursing procedures; 46 to incorrect handling of therapeutic and diagnostic devices; 37 to alarms/warnings of devices used incorrectly; and 131 to failure in data recording by nurses. CONCLUSION: The occurrence of adverse events in the care given to patients by the nursing team are significant indicators that disclose the quality of nursing care. Therefore, these events should be analyzed to support in-service training of the nursing staff.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):276-282
DOI 10.1590/S0103-507X2009000300007
OBJECTIVE: The understanding of adverse events may simplify the inquiry regarding the quality of nursing care, presuming a foregrounding role in evaluating health services. The aim of the study was to identify adverse events in nursing care in an intensive care unit. METHODS: Data were collected using an appropriate form known as problem-oriented record (POR) over a 10-month period; patients were monitored throughout their intensive care unit stay. RESULTS: Over the study period, 550 adverse events were recorded as follows: 26 concerned the "five rights" related to drug administration; 23 to non-administered medication; 181 to inappropriate medication records; 28 to failure in infusion pump assembly; 17 to not performed inhalation; 8 to incorrect handling of needles and syringes; 53 to not performed nursing procedures; 46 to incorrect handling of therapeutic and diagnostic devices; 37 to alarms/warnings of devices used incorrectly; and 131 to failure in data recording by nurses. CONCLUSION: The occurrence of adverse events in the care given to patients by the nursing team are significant indicators that disclose the quality of nursing care. Therefore, these events should be analyzed to support in-service training of the nursing staff.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):283-291
DOI 10.1590/S0103-507X2009000300008
OBJECTIVES: The intensive care unit emerged to improve and concentrate material and human resources for the care of critical patients, and need for constant observation and continuous assistance. However, patients in intensive care unit requires exceptional care, directed not only to the physiopathological problem, but also towards the psychosocial issue, now intimately interlinked to the physical disease. In this ambient, very demanding for capability of the multiprofessional team, presence of the physiotherapist has become more frequent. This study aims to verify if the attitude of an experienced physiotherapist in the intensive care unit is humanized. METHODS: To evaluate physiotherapy care humanization, a questionnaire was prepared and patients over 18 years of age, lucid and staying in intensive care unit for 24 hours or more were included. RESULTS: Forty four patients were interviewed and 95.5% of these considered the physiotherapy care as humanized. Positive association was observed between dissatisfaction with the items of dignity, communication, warranty and empathy, and a dehumannized physiotherapy care. Patients who evaluated warranty as negative had a twofold greater chance (0.7 - 5.3) of perceiving care as dehumanized. Patients who evaluated empathy as negative had a 1.6 (0.8 - 3.4) times greater chance of perceiving care as dehumanized. CONCLUSION: Physiotherapy care given in the intensive care unit was marked by good assistance, attention provided to the patient and quality of treatment, characterizing humanized care.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):283-291
DOI 10.1590/S0103-507X2009000300008
OBJECTIVES: The intensive care unit emerged to improve and concentrate material and human resources for the care of critical patients, and need for constant observation and continuous assistance. However, patients in intensive care unit requires exceptional care, directed not only to the physiopathological problem, but also towards the psychosocial issue, now intimately interlinked to the physical disease. In this ambient, very demanding for capability of the multiprofessional team, presence of the physiotherapist has become more frequent. This study aims to verify if the attitude of an experienced physiotherapist in the intensive care unit is humanized. METHODS: To evaluate physiotherapy care humanization, a questionnaire was prepared and patients over 18 years of age, lucid and staying in intensive care unit for 24 hours or more were included. RESULTS: Forty four patients were interviewed and 95.5% of these considered the physiotherapy care as humanized. Positive association was observed between dissatisfaction with the items of dignity, communication, warranty and empathy, and a dehumannized physiotherapy care. Patients who evaluated warranty as negative had a twofold greater chance (0.7 - 5.3) of perceiving care as dehumanized. Patients who evaluated empathy as negative had a 1.6 (0.8 - 3.4) times greater chance of perceiving care as dehumanized. CONCLUSION: Physiotherapy care given in the intensive care unit was marked by good assistance, attention provided to the patient and quality of treatment, characterizing humanized care.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):292-298
DOI 10.1590/S0103-507X2009000300009
BACKGROUND AND OBJECTIVES: An inspired oxygen fraction (FiO2) of 40% is often used for weaning patients, but lower FiO2 values are also recommended, if arterial oxygen pressure (PaO2)/ FiO2 >150-200 mmHg. This study aimed to compare respiratory variables and vital data values recorded during use of sufficient FiO2 (ideal) to maintain peripheral oxygen saturation at 92% with values recorded during use of FiO2 established at 40% (baseline) in weaning patients. METHODS: Prospective cross-over study. Respiratory variables (respiratory frequency, tidal volume, occlusion pressure, inspiratory time/total time ratio) and vital data (blood pressure and heart rate) were collected sequentially at 30 and 60 minutes with baseline FiO2, followed by ideal FiO2. These were compared to a generalized linear model for repeated measurements. Comparisons between baseline and ideal FiO2 values, and arterial blood gases were evaluated by the Student's t or Wilcoxon tests. RESULTS: In 30 adult patients the median of ideal FiO2 was 25% (IQ25%-75% 23-28). This was significantly lower than baseline FiO2 (40%) (p< 0.001). No significant difference was found in the PaO2/ FiO2 ratio between baseline FiO2 (269±53) and ideal FiO2 (268±47). Tidal volume was significantly lower during use of ideal FiO2 (p=0.003) and blood pressure was significantly higher during use of baseline FiO2 (p=0.041), but there was no clinical significance. The remaining variables were not affected by reduction in FiO2. The ideal FiO2 did not influence remaining variables. CONCLUSIONS: These results suggest that FiO2 levels sufficient to ensure a SpO2>92% did not alter breathing patterns or trigger clinical changes in weaning patients.
Abstract
Revista Brasileira de Terapia Intensiva. 2009;21(3):292-298
DOI 10.1590/S0103-507X2009000300009
BACKGROUND AND OBJECTIVES: An inspired oxygen fraction (FiO2) of 40% is often used for weaning patients, but lower FiO2 values are also recommended, if arterial oxygen pressure (PaO2)/ FiO2 >150-200 mmHg. This study aimed to compare respiratory variables and vital data values recorded during use of sufficient FiO2 (ideal) to maintain peripheral oxygen saturation at 92% with values recorded during use of FiO2 established at 40% (baseline) in weaning patients. METHODS: Prospective cross-over study. Respiratory variables (respiratory frequency, tidal volume, occlusion pressure, inspiratory time/total time ratio) and vital data (blood pressure and heart rate) were collected sequentially at 30 and 60 minutes with baseline FiO2, followed by ideal FiO2. These were compared to a generalized linear model for repeated measurements. Comparisons between baseline and ideal FiO2 values, and arterial blood gases were evaluated by the Student's t or Wilcoxon tests. RESULTS: In 30 adult patients the median of ideal FiO2 was 25% (IQ25%-75% 23-28). This was significantly lower than baseline FiO2 (40%) (p< 0.001). No significant difference was found in the PaO2/ FiO2 ratio between baseline FiO2 (269±53) and ideal FiO2 (268±47). Tidal volume was significantly lower during use of ideal FiO2 (p=0.003) and blood pressure was significantly higher during use of baseline FiO2 (p=0.041), but there was no clinical significance. The remaining variables were not affected by reduction in FiO2. The ideal FiO2 did not influence remaining variables. CONCLUSIONS: These results suggest that FiO2 levels sufficient to ensure a SpO2>92% did not alter breathing patterns or trigger clinical changes in weaning patients.