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ABSTRACT: Respiratory insufficiency is a serious threat to patients with Pompe disease, a neuromuscular disorder caused by lysosomal acid alpha-glucosidase deficiency. Innovative therapeutic options which may stabilize pulmonary function have recently become available. We therefore determined proportion and severity of pulmonary involvement in patients with Pompe disease, the rate of progression of pulmonary dysfunction, and predictive factors for poor respiratory outcome. In a single-center, prospective, cohort study, we measured vital capacity (VC) in sitting and supine positions, as well as maximum inspiratory (MIP) and expiratory (MEP) mouth pressures, and end expiratory CO(2) in 17 children and 75 adults with Pompe disease (mean age 42.7 years, range 5-76 years). Seventy-four percent of all patients, including 53% of the children, had some degree of respiratory dysfunction. Thirty-eight percent had obvious diaphragmatic weakness. Males appeared to have more severe pulmonary involvement than females: at a group level, their mean VC was significantly lower than that of females (p<0.001), they used mechanical ventilation more often than females (p=0.042) and the decline over the course of the disease was significantly different between males and females (p=0.003). Apart from male gender, severe skeletal muscle weakness and long disease duration were the most important predictors of poor respiratory status. During follow-up (average 1.6 years, range 0.5-4.2 years), three patients became ventilator dependent. Annually, there were average decreases in VC in upright position of 0.9% points (p=0.09), VC in supine position of 1.2% points (p=0.049), MIP of 3.2% points (p=0.018) and MEP of 3.8% points (p<0.01). We conclude that pulmonary dysfunction in Pompe disease is much more common than generally thought. Males, patients with severe muscle weakness, and those with advanced disease duration seem most at risk.
Molecular Genetics and Metabolism 06/2011; 104(1-2):129-36. · 3.19 Impact Factor
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ABSTRACT: The majority of patients with severe chronic obstructive pulmonary disease (COPD) have flow limitation, which has deleterious side effects. If these patients are mechanically ventilated, this often results in difficult weaning. Spontaneously breathing COPD patients experience a beneficial effect of pursed lip breathing. We investigated whether in intubated COPD patients application of an external resistance could produce the same beneficial effects on breathing pattern and gas-exchange as pursed lip breathing.
Ten COPD patients with flow limitation were studied during pressure support mechanical ventilation. Two types of expiratory resistances were applied: one fixed level of resistance and one with a resistive pressure decay. Each resistance was applied in 5 patients and the highest level was chosen that did not cause hyperinflation. Blood gas values and breathing pattern with and without resistance were compared.
With resistance 1, gas-exchange and breathing pattern did not change significantly; average PCO2 changed from 8.0 to 8.1 kPa, PO2 from 10.2 to 10.3 kPa, tidal volume from 0.380 to 0.420 l, respiratory rate from 25 to 23 bpm and inspiratory:expiratory ratio from 1:1.9 to 1:2.0. With resistance 2, gas-exchange and breathing pattern did not change significantly; average PCO2 changed from 5.8 to 6.0 kPa, PO2 from 11.1 to 12.1 kPa, tidal volume from 0.733 to 0.695 l, respiratory rate from 16 to 18 bpm and inspiratory:expiratory ratio from 1:2.3 to 1:2.9.
In intubated COPD patients being weaned from the ventilator, application of an external resistance did not have the same beneficial effects as pursed lip breathing.
Acta Anaesthesiologica Scandinavica 11/2001; 45(9):1155-61. · 2.19 Impact Factor
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ABSTRACT: In severe chronic obstructive pulmonary disease (COPD) lung emptying is disturbed by airways compression and expiratory flow limitation. Application of an external resistance has been suggested to counteract airways compression and improve lung emptying. We studied the effect of various resistance levels on lung emptying in mechanically ventilated COPD patients. In 18 patients an adjustable resistor was applied. The effect on airways compression was assessed by iso-volume pressure--flow curves (IVPF) and by interrupter measurements. Respiratory mechanics during unimpeded expirations were correlated to the results obtained with the resistances. The resistances caused an increase in iso-volume flow at the IVPF-curves in six patients, indicating that airways compression was counteracted. Interrupter measurements showed that overshoots in flow (as measure of flow limitation) were significantly reduced by the resistor. These effects could be predicted on basis of respiratory mechanics during unimpeded expiration. In conclusion, mechanically ventilated COPD patients can be identified in whom application of external resistances counteracts airways compression and reduces flow limitation.
Respiration Physiology 09/2001; 127(1):39-52.
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ABSTRACT: In mechanically ventilated patients, the expiratory time constant provides information about the respiratory mechanics and the actual time needed for complete expiration. As an easy method to determine the time constant, the ratio of exhaled tidal volume to peak expiratory flow has been proposed. This assumes a single compartment model for the whole expiration. Since the latter has to be questioned in patients with chronic obstructive pulmonary disease (COPD), we compared time constants calculated from various parts of expiration and related these to time constants assessed with the interrupter method.
Prospective study.
A medical intensive care unit in a university hospital.
Thirty-eight patients (18 severe COPD, eight mild COPD, 12 other pathologies) were studied during mechanical ventilation under sedation and paralysis.
Time constants determined from flow-volume curves at 100%, the last 75, 50, and 25% of expired tidal volume, were compared to time constants obtained from interrupter measurements. Furthermore, the time constants were related to the actual time needed for complete expiration and to the patient's pulmonary condition. The time constant determined from the last 75% of the expiratory flow-volume curve (RCfv75) was in closest agreement with the time constant obtained from the interrupter measurement, gave an accurate estimation of the actual time needed for complete expiration, and was discriminative for the severity of COPD.
In mechanically ventilated patients with and without COPD, a time constant can well be calculated from the expiratory flow-volume curve for the last 75% of tidal volume, gives a good estimation of respiratory mechanics, and is easy to obtain at the bedside.
Intensive Care Medicine 12/2000; 26(11):1612-8. · 5.40 Impact Factor
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ABSTRACT: To assess the feasibility of expiratory flow-volume curves as a measurement of respiratory mechanics during ventilatory support: to what extent is the shape of the curve affected by the exhalation valve of the ventilator?
Prospective, comparative study.
Medical intensive care unit of a university hospital.
28 consecutive patients with various conditions, mechanically ventilated with both the Siemens Servo 900C and 300 ventilators, were studied under sedation and paralysis.
The ventilator circuit was intermittently disconnected from the ventilator at end-inspiration in order to obtain flow-volume curves with and without the exhalation valve in place.
Peak flow (PEF) and the slope of the flow-volume curve during the last 50 % of expired volume (SF50) were obtained both with and without the exhalation valve in place. The exhalation valve caused a significant reduction in peak flow of 0.3 l/s (from 1.27 to 0.97 l/s) with the Siemens Servo 900 C ventilator and of 0.42 l/s (from 1.36 to 0.94 l/s) with the Siemens Servo 300 ventilator (p < 0.001). The SF50 was not affected.
In mechanically ventilated patients, the exhalation valve causes a significant reduction in peak flow, but does not affect the SF50. This study further suggests that the second part of the expiratory flow-volume curve can be used to estimate patients' respiratory mechanics during ventilatory support.
Intensive Care Medicine 09/1999; 25(8):799-804. · 5.40 Impact Factor
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ABSTRACT: Forced expiratory flow-volume curves are commonly used to assess the degree of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). In mechanically ventilated subjects, expiratory airways obstruction can only be estimated from relaxed expirations. The aim of this study was to quantify the degree of airways obstruction from relaxed expiratory flow-volume curves in mechanically ventilated patients with COPD.
As measure of airflow obstruction, the effective time constant during the last 50% of expired volume (tau) was calculated. For bedside monitoring, tau was recalculated as the slope of the flow during the last 50% of expired volume (SF50). In order to study reproducibility, the variables were calculated from consecutive breaths and at different levels of end-expiratory lung volume (EEV). The SF50 and the tau-were correlated with the forced expiratory volume in 1 s (FEV1) measured prior to the start of ventilatory support.
Twenty-seven patients were studied with a FEV1 expressed as percentage predicted of 31 +/- 12% (mean +/- SD). The SF50 amounted to 19 +/- 10 degrees. A positive linear correlation was established between SF50 and the FEV1, (%pred), (r = 0.90, P < 0.0001). The tau showed an exponential relationship with FEV1 (%pred), (r2 = 0.78). From 5 consecutive breaths the mean variation coefficient of SF50 was 5 +/- 2%. Changes of delta EEV from 0.05 to 1.00 L did not affect the SF50-values. In 12 patients, mechanically ventilated for respiratory diseases other than COPD, mean tau and SF50 were significantly different from the COPD-patients (P < 0.0001).
This study indicates that relaxed expiratory flow-volume curves can be used to assess airflow obstruction in mechanically ventilated patients with COPD. This information can be used to adapt ventilatory settings.
Acta Anaesthesiologica Scandinavica 03/1999; 43(3):322-7. · 2.19 Impact Factor
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ABSTRACT: The effects of continuous positive airway pressure (CPAP) provided by the Siemens Servo 900C ventilator were compared with a continuous flow system (CF-CPAP) in patients weaning from the ventilator. Thirteen patients were studied using both systems at a CPAP level of 0.5 kPa. Additional work of breathing (Wapp) and derived variables were determined in relation to the minute volumes of the patients. The Wapp imposed by the ventilator exceeded the Wapp of CF-CPAP in all patients. The difference in Wapp between ventilator- and CF-CPAP was greater at higher ventilatory needs. The increments in Wapp imposed by the ventilator were positively correlated with the actual end-expiratory pressures (EEP). The EEP increasingly exceeded the preset CPAP level of the ventilator at higher minute volumes. An inspiratory threshold due to a gradient between EEP and preset CPAP greatly increased the Wapp imposed by the ventilator. As this threshold was attributed to the resistance of the PEEP device of the ventilator, it indicates that the additional work related to the expiratory value should be taken into account when the Siemens Servo 900C ventilator is used for weaning purposes.
Anaesthesia and intensive care 11/1997; 25(5):487-92. · 1.28 Impact Factor
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ABSTRACT: Continuous positive airway pressure (CPAP) is known to decrease inspiratory work of breathing in patients with chronic obstructive pulmonary disease (COPD). This effect is primarily attributed to a reduction in inspiratory elastic work of breathing (Wi,el) related to a decrease in intrinsic positive end-expiratory pressure (PEEP).
The aim of this study is to design a model for computation of Wi,el on the basis of respiratory mechanics in patients with COPD, at various intrinsic PEEP- and CPAP-levels. The model was used to estimate the optimal CPAP-level with respect to the intrinsic PEEP-level in terms of reduction of Wi,el. Calculations of the decrease in Wi,el due to CPAP obtained with the model were compared to changes in Wi,el and total work of breathing (Wi,tot) determined from respiratory measurements in patients with COPD.
Model calculations revealed that Wi,el was minimal whenever a CPAP-level equal to the intrinsic PEEP-level was applied. When a CPAP-level exceeding the intrinsic PEEP-level was applied, the reduction in Wi,el was less. Comparing these results to the respiratory measurements, a similar pattern in reduction of Wi,el and Wi,tot was established, although absolute values of the differences were smaller in the experimental data.
This study indicates that in order to reduce Wi,el in patients with COPD, intrinsic PEEP should be measured and the CPAP-level adjusted to the intrinsic PEEP-level.
Acta Anaesthesiologica Scandinavica 06/1997; 41(5):607-13. · 2.19 Impact Factor
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ABSTRACT: In patients with severe chronic obstructive pulmonary disease (COPD), lung emptying may be affected by flow limitation. We tested the hypothesis that the airway compression leading to flow limitation can be counteracted by controlling the expiratory flow. The effects of an external resistor on lung emptying were studied in six patients with COPD, who were mechanically ventilated whilst sedated and paralysed. Respiratory mechanics were obtained during ventilatory support with and without the resistor. Airway compression was assessed using the interruptor method. For the study, a turbulent resistor was applied with the highest resistance level that did not increase the end-expiratory lung volume. At this resistance level, external positive end-expiratory pressure (PEEP) was generated in all patients. As total PEEP levels remained unchanged at both settings during the controlled expiration, the levels of intrinsic PEEP were significantly decreased from 0.96+/-0.30 to 0.53+/-0.19 kPa (mean+/-SD). Comparison of the expiratory flow-volume curves at both settings revealed that, during the controlled expiration, the flows were significantly decreased during the first 40% of the expired volume and significantly increased during the last 60%. As the end-expiratory lung volumes remained unchanged during both settings, these increments in flow indicated a decrease in effective resistance. Airway compression was observed during unimpeded expirations in all patients using the interruptor method. During the application of the resistor, airway compression was no longer detectable. In patients with chronic obstructive pulmonary disease receiving ventilatory support, the application of an external resistor could decrease effective expiratory resistance by counteracting airway compression, without increments in end-expiratory lung volume.
European Respiratory Journal 04/1997; 10(3):550-6. · 5.89 Impact Factor
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ABSTRACT: We reported the case of a patient in whom severe, and ultimately fatal, pulmonary hypertension developed 1.5 yrs after transjugular intrahepatic portosystemic shunt (TIPS). Pulmonary artery pressures were not affected by 100% oxygen, prostacyclin or nifedipine. Postmortem examinations showed pulmonary and vascular abnormalities typical of pulmonary hypertension. Pulmonary artery pressures should be measured in each patient with otherwise not readily explained dyspnoea following transjugular intrahepatic portosystemic shunt.
European Respiratory Journal 08/1996; 9(7):1562-4. · 5.89 Impact Factor
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ABSTRACT: In patients with airflow obstruction, flow limitation can be established in various ways. Using body plethysmography, flow limitation is assumed when expiratory flow decreases whilst alveolar pressure increases at the same time. During forced expiration, flow limitation can be established by means of the flow interruptor technique; flow limitation is assumed when, after release of an occlusion, a spike flow superimposed on the ongoing alveolar flow (delta peak flow) is detected. In this study, the flow interruptor technique was applied to detect flow limitation during tidal breathing. The results were compared to those obtained with the body plethysmograph. The expiratory flow pattern, post-interruption, was analysed in 33 subjects; 11 patients with airflow obstruction and flow limitation established with the body plethysmograph (AO+); 11 patients with airflow obstruction without flow limitation (AO-); and 11 healthy volunteers. Mean spike areas were 27.6 +/- 18.3, 4.6 +/- 2.3 and 3.4 +/- 2.0 mL for the AO+, AO- and control group, respectively, showing a highly significant difference between the AO+ patients and the other groups. Also, significantly higher delta peak flows were found in the AO+ patients compared to the other groups. No differences in delta peak flows or spike areas could be established between patients without flow limitation and controls. We conclude that the interruptor technique may be a useful means of assessing flow limitation during tidal breathing.
European Respiratory Journal 12/1995; 8(11):1910-4. · 5.89 Impact Factor
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ABSTRACT: The application of continuous positive airway pressure (CPAP) is known to reduce inspiratory work of breathing in intubated patients with chronic obstructive pulmonary disease (COPD). This effect is caused by a decrease in elastic work related to a reduction in intrinsic PEEP. The aim of this study was to relate the decrease in inspiratory work due to CPAP to the intrinsic PEEP levels obtained during spontaneous breathing without positive pressure. Ten intubated patients with COPD who had been ventilated for acute respiratory failure were studied. Intrinsic PEEP was determined during tracheal occlusions performed at end-expiration when the patient was breathing without positive airway pressure. Inspiratory work was computed during breathing through a circuit with a CPAP of 0.5 kPa and the same circuit without positive pressure. Intrinsic PEEP-levels ranged from 0.26 to 1.31 kPa. Compared to spontaneous breathing without positive pressure, CPAP reduced the total inspiratory work per liter of ventilation (Wltot) from 1.42 +/- 0.48 to 1.24 +/- 0.50 J.1-1 (means +/- SD P < 0.01). This decrease was found to be related to the intrinsic PEEP-levels; the largest reductions were found in the patients with an intrinsic PEEP-level close to the CPAP-level applied. In intubated patients with COPD, the decrease in Wltot due to a CPAP of 0.5 kPa was found to be related to the intrinsic PEEP-levels present when no positive airway pressure was applied. The intrinsic PEEP measured during tracheal occlusions could be used to estimate the effect of CPAP in these patients.
Acta Anaesthesiologica Scandinavica 11/1995; 39(8):1097-102. · 2.19 Impact Factor
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ABSTRACT: To study whether high fat, low carbohydrate enteral nutrition could reduce VCO2 in patients during ventilator support and weaning from the ventilator in order to facilitate the weaning process.
prospective, randomized controlled study.
Medical ICU of a university hospital.
32 ventilator-dependent patients with a prospect of weaning from mechanical ventilation.
high fat feeding administered to 15 patients and standard isocaloric feeding administered to 17 patients, both in a dosage of 1.5 times basal metabolic rate.
Respiratory and metabolic measurements were obtained both during mechanical ventilation and weaning procedures. High fat feeding was associated with significantly lower RQ values compared with standard feeding; the mean (+/- SEM) RQ values during mechanical ventilation amounted to 0.91 +/- 0.01 and 1.00 +/- 0.02 and during weaning to 0.72 +/- 0.02 and 0.86 +/- 0.02 for high fat and standard nutrition respectively (both p-values < 0.001). High fat feeding reduced the CO2-excretion both during mechanical ventilation and weaning, but only the decrease during weaning proved to be significant; the mean (+/- SEM) CO2-excretion amounted to 0.177 +/- 0.010 and 0.231 +/- 0.011 1/min STPD for the high fat and standard feeding respectively (p < 0.01). No significant differences were found in the PaCO2 during weaning between the two feeding groups.
High fat, low carbohydrate enteral feeding significantly reduced the RQ values in ventilated patients with decreases in VCO2, but in this study failed to reduce PaCO2 during weaning from the ventilator.
Intensive Care Medicine 09/1994; 20(7):470-5. · 5.40 Impact Factor
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ABSTRACT: We studied the effects of positive end-expiratory pressure (PEEP) applied by the ventilator on respiratory mechanics in ventilated patients with chronic obstructive pulmonary disease (COPD). Airway pressures, relaxed expiratory flow-volume curves and end-expiratory volumes (EEV) were measured. In all patients investigated without PEEP applied by the ventilator, an intrinsic PEEP level (PEEPi) and a concavity in the flow-volume curve was present. Ventilator-PEEP caused a significant decrease in PEEPi in all patients (p less than 0.01). In patients in whom ventilator-PEEP exceeded PEEPi, significant increases occurred in airway pressures and EEV (p less than 0.05) and moreover the shape of the flow-volume curve was changing. In patients in whom the level of ventilator-PEEP was below the PEEPi level, no significant changes in airway pressures, EEV or flow-volume curves were found. We conclude: 1) PEEP applied by the ventilator can reduce PEEPi in ventilated patients with COPD without significant changes in airway pressures, EEV or flow-volume curves. 2) Expiratory flow-volume curves can be used to estimate the effects of ventilator-PEEP on EEV.
European Respiratory Journal 06/1991; 4(5):561-7. · 5.89 Impact Factor
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ABSTRACT: The effect of enteral nutrition with different protein contents on metabolic and ventilatory variables during weaning from the ventilator was studied in 10 mechanically ventilated patients as indication of the effect of protein on the ventilatory drive. Resting energy expenditure (R.E.E.) was assessed in the post-absorptive state and 2 enteral regimens both with a fat and carbohydrate content 1.25 times R.E.E. but with a moderate (190 mg N/kg/24 h) and high (260 mgN/kg/24 h) protein content were given to the patients in random order. Minute ventilation (V(E)), CO2-production (VCO2), O2-consumption (VO2) and arterial blood-gases were obtained during mechanical ventilation and weaning. Compared with post-absorptive state, both intakes gave significant increases in VCO2 during mechanical ventilation; the VCO2 values were equal for both regimens before the start of the weaning procedures. High protein intake was associated with significantly higher VCO2 during weaning and smaller increases in paCO2 from mechanical ventilation to the end of the weaning-period, compared with the moderate protein intake. This result is in agreement with studies in which an infusion of amino-acids in spontaneous breathing healthy volunteers increased ventilatory sensitivity to CO2. For mechanically ventilated patients high protein nutrition may be beneficial in enhancing weaning from the ventilator.
Clinical Nutrition 09/1989; 8(4):207-12. · 3.73 Impact Factor
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Nederlands tijdschrift voor geneeskunde 11/1988; 132(42):1934-6.
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ABSTRACT: The occurrence of pulmonary oedema was studied retrospectively in 243 patients who underwent pneumonectomy in one hospital from 1975 to 1984. Pulmonary oedema developed in eight of 113 patients who had a right sided pneumonectomy and in three of 130 patients undergoing a left sided procedure. It occurred more commonly in patients requiring a second thoracotomy because of blood loss (in three out of seven patients). There were no significant differences preoperatively in pulmonary function, lung perfusion scans, or cardiovascular condition between patients who subsequently developed pulmonary oedema and those who did not. Postoperative fluid balance was significantly more positive in patients developing pulmonary oedema than in those not developing oedema. Thus pulmonary oedema was associated with right sided pneumonectomy, repeat thoracotomy, and more positive fluid balance.
Thorax 05/1988; 43(4):323-6. · 6.84 Impact Factor
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ABSTRACT: The effect of enteral feeding on O2-consumption (VO2) and CO2-production (VCO2) was studied in 9 ventilator-dependent patients, who were in a stable condition without signs of hypermetabolism. Resting energy expenditure (REE) in postabsorptive state was assessed and enteral feeding was started by continuous drip (480 kcal carbohydrate, 360 kcal vegetable fat and 160 kcal milkprotein: 6.4 g Nitrogen/1000 ml). Patients were given a moderate and a high caloric intake: 1.5 and 2.0 times REE. VO2 and VCO2 were measured for a 24 h period, beginning 7 h after the start of the dietary intake. Significant greater increases in VO2, VCO2 and RQ were found during high caloric intake compared with the moderate caloric intake. VO2, VCO2 and arterial blood-gases were measured in 4 patients during weaning from the ventilator. The increase in VCO2 induced by the high caloric feeding resulted in a rise in arterial CO2 tension (PaCO2) and respiratory distress. High caloric enteral nutrition can cause a significant increase in VCO2 inducing respiratory distress during weaning from the ventilator in patients with limited pulmonary reserves. Moderate caloric nutrition will be preferable to these patients in order to facilitate the weaning.
Intensive Care Medicine 02/1988; 14(3):206-11. · 5.40 Impact Factor
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ABSTRACT: Energy expenditure and the amount of metabolised carbohydrate, protein and lipid can be calculated from the O2 consumption, CO2 production and nitrogen excretion using indirect calorimetry. A low-cost automatic system has been developed suitable for short- and long-term measurements during artificial ventilation, in which the gas analysers were calibrated automatically every 10 min and in which the desired variables were calculated and printed every 5 min. O2 and CO2 concentrations of mixed expired and inspiratory gas, the expired minute volume VE, and patient's rectal temperature, were sampled at regular time intervals and a simple programmable calculator with printer was used for the on-line data analysis. Tests on accuracy, stability, reproducibility and feasibility showed this system to be suitable for clinical application.
Clinical Physics and Physiological Measurement 09/1987; 8(3):261-9.
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ABSTRACT: The effect of enteral nutrition with different protein contents on metabolic and ventilatory variables during weaning from the ventilator was studied in 10 mechanically ventilated patients as indication of the effect of protein on the ventilatory drive. Resting energy expenditure (R.E.E.) was assessed in the post-absorptive state and 2 enteral regimens both with a fat and carbohydrate content 1.25 times R.E.E. but with a moderate (190 mg N/kg/24 h) and high (260 mgN/kg/24 h) protein content were given to the patients in random order. Minute ventilation (V̇E), CO2-production (V̇CO2), O2-consumption (V̇O2) and arterial blood-gases were obtained during mechanical ventilation and weaning. Compared with post-absorptive state, both intakes gave significant increases in V̇CO2 during mechanical ventilation; the V̇CO2 values were equal for both regimens before the start of the weaning procedures. High protein intake was associated with significantly higher V̇CO2 during weaning and smaller increases in paCO2 from mechanical ventilation to the end of the weaning-period, compared with the moderate protein intake. This result is in agreement with studies in which an infusion of amino-acids in spontaneous breathing healthy volunteers increased ventilatory sensitivity to CO2. For mechanically ventilated patients high protein nutrition may be beneficial in enhancing weaning from the ventilator.
Clinical Nutrition.
