Online Brief Report
Increase in Oxygen Consumption After Albuterol Inhalation in Ventilated Infants and Children Patrick A. Ross, MD; Christopher J. L. Newth, MD, FRCPC; Cindy A. C. Hugen, MD; John K. Maher, MD; Timothy W. Deakers, MD, PhD
Objective: To determine if inhaled albuterol (salbutamol) increases oxygen consumption (V′o2) in children and, if so, the duration of this effect. Design: Oxygen consumption was measured by indirect calorimetry using the Argon dilution technique with a respiratory mass spectrometer. After measurement of baseline values, albuterol was administered and subsequent measurements were performed at 10 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. Setting: Multidisciplinary PICU in a university teaching hospital. Patients: Eleven intubated infants and children (five girls, six boys) with a mean age of 20 months (range, 1 mo to 8 yr) and a mean weight of 10.7 kg (range, 3.1–23 kg) who required therapeutic albuterol inhalations. Intervention: Nine hundred micrograms of albuterol (10 puffs) was administered by a metered-dose inhaler into a spacer through the inspiratory arm of the ventilator circuit near to the patient, during 10 mechanically assisted breaths. Measurements and Main Results: All children showed an increase in V′o2 within 10 minutes (mean increase 48.6%). The increased V′o2 was still elevated (42.3% above baseline) at 1 hour, but 3 hours after albuterol inhalation, the V′o2 was back to baseline in all patients. Heart rate increased significantly at 10 minutes, 1 hour, and 2 hours after inhalation. Conclusion: There is a large increase in V′o2 after albuterol inhalation. This effect lasts up to 3 hours. (Pediatr Crit Care Med 2014; 15:e389–e392) All authors: Division of Critical Care, Children’s Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, CA. Current address for Dr. Hugen: Department of Respiratory Medicine and Allergy, Radboud University Nijmegen Medical Centre, Amalia Children’s Hospital, Nijmegen, The Netherlands. Current address for Dr. Maher: Division of Critical Care, Driscoll Children’s Hospital, Corpus Christi, TX. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Patrick A. Ross, MD, PICU Administration, MS #12, Children’s Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027. E-mail: [email protected] Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000000279
Pediatric Critical Care Medicine
Key Words: albuterol inhalation; bronchodilator; children; mechanical ventilation; oxygen consumption; salbutamol
I
nhaled albuterol, a β-agonist, is widely used in the management of asthma in children. Recent reports have shown elevated serum lactate levels in children receiving albuterol for asthma (1–3). The elevated lactate occurred in the presence of normal oxygen delivery leading the authors to question whether the effect was due to β-adrenergic stimulation (2). It has been known for some time that epinephrine (adrenaline) and albuterol (salbutamol) have a stimulating effect in human adults on minute volume of ventilation (V′E) and oxygen consumption (V′o2) (4–7). We have previously demonstrated a marked increase in V′E (mean, 82%) and V′o2 (mean, 46.5%) in anesthetized, intubated, and spontaneously breathing Rhesus monkeys after inhalation of albuterol (8). This metabolic response appeared to be a “class” effect of β-adrenergic drugs as it occurred after several additional β-agonists but was not seen after ipratropium bromide, cromolyn sodium, or theophylline (8). Further, the metabolic response to albuterol in the Rhesus monkey was fully suppressed by the nonselective β-adrenergic blocker, propranolol (9). The effect of albuterol on oxygen consumption has not been previously reported in children. The aim of this study was to determine if inhaled albuterol increases oxygen consumption in infants and children and, if so, the duration of this effect.
MATERIALS AND METHODS This study was conducted in a multidisciplinary PICU on 11 infants and children who required therapeutic albuterol inhalations. Only children with cuffed endotracheal tubes (ETTs) were included because an absence of an air leak was needed for accurate measurements of gas exchange. The patients received sedation titrated to adequate effect based on nursing and physician observation. The study was approved by the investigational review board, and informed consent was obtained from the parents in each case. Oxygen consumption (V′o2), carbon dioxide production (V′co2), minute ventilation (V′E), and respiratory quotient www.pccmjournal.org
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Ross et al
were measured by indirect calorimetry using the Argon dilution technique with a respiratory mass spectrometer (Airspec MGA 2200, Biggin Hill, United Kingdom) (10). We have previously reported the measurement of expired gases from the ETT using an isolation valve in this manner (11–13). Vital signs were recorded including heart rate, respiratory rate, oxygen saturation by pulse oximetry, end-tidal carbon dioxide, and temperature by rectal probe. After measurement of baseline values, 900 μg of albuterol (10 puffs) was administered by a metered-dose inhaler into a spacer (A.C.E. Diemolding Healthcare Division, Canastota, NY) (14) through the inspiratory arm of the ventilator circuit near to the patient, during 10 mechanically assisted breaths. Subsequent measurements were performed at 10 minutes, 1 hour, 2 hours, 3 hours, and 4 hours after administration.
shows the mean values ± sd, and the mean percent change from baseline, for V′o2, V′E, and heart rate before and 10 minutes, 1 hour, 2 hours, and 3 hours after inhalation of albuterol. Data are presented only to 3 hours as mean values had returned to baseline. Changes in V′o2, V′E, and heart rate are presented graphically in Figure 1. Following albuterol inhalation, there was an increase in V′o2 within 10 minutes for all patients. V′o2 was increased further at the 1-hour measurement and returned to baseline by 3 hours. The change in V′o2 was statistically significant at 10 minutes and 1 hour after albuterol inhalation. The heart rate was increased significantly at 10 minutes, 1 hour, and 2 hours after albuterol. No significant changes in V′E were found.
Statistical Analysis Mean percent changes between baseline and post inhalation values were compared by analysis of variance with Bonferroni correction (Statistica, Microsoft Corporation, Richmond, WA). Each patient served as his or her own control. A p value less than or equal to 0.05 was considered significant.
This study demonstrates that inhaled albuterol causes a marked increase in oxygen consumption in infants and children. This is consistent with previous observations in monkeys (8, 9) and adults (6). The increase of V′o2 within 10 minutes was rapid but consistent with reports on the pharmacokinetics of albuterol (15). The maximum increase in V′o2 was reached in all subjects by 1 hour. The duration of the effect was, on average, complete by 3 hours although in some individuals lasted up to 4 hours. The increase in heart rate followed a similar pattern, but the increase was significant up to 2 hours. The change in heart rate was not a novel finding but showed that the method for administration with albuterol in the ventilator circuit was effective. The absence of a change in V′E probably occurred as a result of the patients being studied were either sedated while
RESULTS Eleven children were included, five girls and six boys. The mean age was 20 months, with a range from 1 month to 8 years. Their mean weight was 10.7 kg (range, 3.1–23 kg). Table 1 shows the patient characteristics. All patients were on low ventilator settings, with an Fio2 of 0.45 or less. Table 2 Table 1. Patient
DISCUSSION
Patient Characteristics for 11 Children Receiving Albuterol Sex
Age (yr)
Weight (kg)
Diagnosis
Fio2
Ventilator Settings
Sedation
1
Female
2 1/12
15
Seizures, asthma
0.4
CPAP = 4
Phenobarbital, diazepam
2
Female
2 3/12
16
Pneumonia, RSV+
0.4
CPAP = 4
Morphine, diazepam
3
Female
8 1/12
23
Fibrotic lung disease
0.35
PS = 12; PEEP = 4
Fentanyl, midazolam
4
Male
1/12
3.9
Pneumonia
0.45
SIMV/PC; rate = 12/ min, PIP = 26; PEEP = 4
Morphine, diazepam
5
Male
3/12
6.1
Pneumonia
0.45
SIMV/PC; rate = 16 /min, PIP = 28; PEEP = 4
6
Male
1 5/12
11.6
Pneumonia
0.4
CPAP = 4
Fentanyl, midazolam
7
Female
3/12
5
Pneumonia, RSV+
0.4
CPAP = 4
Fentanyl, midazolam
8
Male
1/12
3.1
Congenital lobar emphysema status post lobectomy
0.4
PS = 8, PEEP = 4; rate = 6/min
9
Female
1 3/12
8.2
Bronchiolitis/RSV + BPD
0.4
CPAP = 2
Fentanyl, midazolam, pentobarbital
10
Male
3 10/12
19.4
Pneumonia
0.4
SIMV/PC; rate = 24/ min, PIP = 34; PEEP = 4
Fentanyl, diazepam, vecuronium
11
Male
1 1/12
6.3
Viral pneumonia, BPD
0.4
PS = 12; rate = 12 / min, PEEP = 6
Fentanyl, midazolam pentobarbital
Diazepam
Morphine
CPAP = continuous positive airway pressure, RSV = respiratory syncytial virus, PS = pressure support, PEEP = positive end-expiratory pressure, SIMV = synchronized intermittent mandatory ventilation, PC = pressure control, PIP = peak inspiratory pressure, BPD = bronchopulmonary dysplasia.
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November 2014 • Volume 15 • Number 9
Online Brief Report
Table 2. Mean Oxygen Consumption, Volume of Ventilation, and Heart Rate (±sd) and Percent Change From Baseline at 10 Minutes, 1 Hour, 2 Hours, and 3 Hours After Inhalation of Albuterol Measurements
Baseline Before Albuterol
10 Min Post Albuterol
1 Hr Post Albuterol
2 Hr Post Albuterol
3 Hr Post Albuterol
Oxygen consumption (mL/min/kg)
8.23 ± 3.95
12.23 ± 6.34
11.71 ± 4.22
9.59 ± 4.7
Δ % (from baseline)
0
48.6a
42.3a
16.5
–14.5
Volume of ventilation (mL/min/kg)
371.0 ± 2.47
390.7 ± 2.37
385.0 ± 2.32
366.4 ± 2.13
361.7 ± 2.01
Δ % (from baseline)
0
5.3
3.8
–1.3
–2.5
121 ± 19
148 ± 18
145 ± 21
143 ± 17
133 ± 17
0
22.3
19.8
18.2
Heart rate (beats/min) Δ % (from baseline)
a
a
a
7.04 ± 4.28
9.9
p < 0.05.
a
Figure 1. Mean percentage change in oxygen consumption (V′o2), minute ventilation, and heart rate 10 min, 1 hr, 2 hr, and 3 hr after inhalation of albuterol. Data were compared by analysis of variance with Bonferroni correction (*p < 0.05). Of note, the significant value at 120 min was heart rate and not V′o2. V′E = volume of ventilation.
breathing spontaneously through the ETT or under neuromuscular blockade on fixed ventilator settings. The large increase in oxygen consumption we found with albuterol use has clinical implications in a PICU setting. Patients with critical asthma who are receiving large doses of albuterol as with a continuous inhalation often have ongoing tachycardia. Further, these patients have been found to have elevated serum lactate levels. It is difficult to identify whether the tachycardia and elevated lactate are related to their disease process or a result of ongoing β-adrenergic stimulation. By increasing oxygen consumption, large doses of albuterol may be causing harm and alternative medications such as Levalbuterol may bear consideration. Potential mechanisms for the increase in V′o2 after albuterol inhalation are the effects of albuterol on bronchi (dilatation) and increasing minute ventilation (7), increasing heart rate (16), Pediatric Critical Care Medicine
glycogenolysis and calorigenesis (17), skeletal muscle tremor (18), and direct effects on cellular metabolism. Albuterol acting at the cellular sodium-potassium-ATPase pump for the treatment of hyperkalemia has been shown to be effective within 30–60 minutes (19, 20). In our present study, albuterol caused a significant increase in heart rate, which may have contributed to the increased V′o2. We did not observe a change in minute ventilation or tremor, and we were unable to measure cellular effects. The results of the study must be viewed in light of possible limitations. There were a limited number of patients enrolled. The disease processes, sedation, and modes of mechanical ventilation varied. We did not attempt to control the patient’s temperature but as is standard in a PICU, room temperature remained constant during the measurements which were completed in 4 hours. The albuterol dosage was higher than others may choose in their clinical practice. However, this is a dose that we used clinically and was chosen to allow for the delivery method and the potential for condensation of drug on the ventilator tubing. One additional limitation is that for patients with asthma, a transient fall in arterial oxygen tension has been observed after inhalation of β2-agonist bronchodilators. The mechanism of this acute decline in oxygenation has been assumed to reflect increased mismatch of ventilation to perfusion. As all of these patients were receiving supplemental oxygen, we cannot assess whether the increase in V′o2 as a direct effect of albuterol could contribute to a fall in arterial oxygen tension. In conclusion, we found a large increase in V′o2 in children receiving inhaled albuterol. The effect was present in 10 minutes and lasted up to 3 hours after a single inhaled dose. Further research will be necessary to determine if this effect contributes to the development of elevate serum lactate or other side effects seen with albuterol use.
REFERENCES
1. Koul PB, Minarik M, Totapally BR: Lactic acidosis in children with acute exacerbation of severe asthma. Eur J Emerg Med 2007; 14:56–58 www.pccmjournal.org
e391
Ross et al 2. Meert KL, McCaulley L, Sarnaik AP: Mechanism of lactic acidosis in children with acute severe asthma. Pediatr Crit Care Med 2012; 13:28–31 3. Walsh SA, Paget RI, Ramnarayan P: Salbutamol usage and lactic acidosis in acute severe asthma. Pediatr Crit Care Med 2013; 14:116–117 4. Leitch AG, Clancy LJ, Costello JF, et al: Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal men. Br Med J 1976; 1:365–367 5. Stretton M, Deakers TW, Newth CJ: The ventilatory and oxygen cost of inhaling drugs used in the therapy of obstructive lung disease. Pediatr Res 1990; 27:36A 6. Amoroso P, Wilson SR, Moxham J, et al: Acute effects of inhaled salbutamol on the metabolic rate of normal subjects. Thorax 1993; 48:882–885 7. Tobin AE, Pellizzer AM, Santamaria JD: Mechanisms by which systemic salbutamol increases ventilation. Respirology 2006; 11:182–187 8. Newth CJ, Amsler B, Anderson GP, et al: The ventilatory and oxygen costs in the anesthetized rhesus monkey of inhaling drugs used in the therapy and diagnosis of asthma. Am Rev Respir Dis 1991; 143:766–771 9. Newth CJ, Amsler B, Richardson BP, et al: The effects of bronchodilators on spontaneous ventilation and oxygen consumption in rhesus monkeys. Pediatr Res 1997; 42:157–162 10. Davies NJ, Denison DM: The measurement of metabolic gas exchange and minute volume by mass spectrometry alone. Respir Physiol 1979; 36:261–267
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11. Sivan Y, Deakers TW, Newth CJ: An automated bedside method for measuring functional residual capacity by N2 washout in mechanically ventilated children. Pediatr Res 1990; 28:446–450 12. Sivan Y, Deakers TW, Newth CJ: Functional residual capacity in ventilated infants and children. Pediatr Res 1990; 28:451–454 13. Sivan Y, Hammer J, Newth CJ: Measurement of high lung volumes by nitrogen washout method. J Appl Physiol (1985) 1994; 77:1562–1564 14. Coleman DM, Kelly HW, McWilliams BC: Determinants of aerosolized albuterol delivery to mechanically ventilated infants. Chest 1996; 109:1607–1613 15. Anderson PJ, Zhou X, Breen P, et al: Pharmacokinetics of (R,S)albuterol after aerosol inhalation in healthy adult volunteers. J Pharm Sci 1998; 87:841–844 16. Tandon MK: Cardiopulmonary effects of fenoterol and salbutamol aerosols. Chest 1980; 77:429–431 17. Holloway BR, Howe R, Rao BS, et al: ICI D7114 a novel selective beta-adrenoceptor agonist which selectively stimulates brown fat and increases whole-body oxygen consumption. Br J Pharmacol 1991; 104:97–104 18. Jenne JW, Valcarenghi G, Druz WS, et al: Comparison of tremor responses to orally administered albuterol and terbutaline. Am Rev Respir Dis 1986; 134:708–713 19. Montoliu J, Lens XM, Revert L: Potassium-lowering effect of albuterol for hyperkalemia in renal failure. Arch Intern Med 1987; 147:713–717 20. Lens XM, Montoliu J, Cases A, et al: Treatment of hyperkalaemia in renal failure: Salbutamol v. insulin. Nephrol Dial Transplant 1989; 4:228–232
November 2014 • Volume 15 • Number 9
Increase in Oxygen Consumption After Albuterol Inhalation in Ventilated Infants and Children Patrick A. Ross, MD; Christopher J. L. Newth, MD, FRCPC; Cindy A. C. Hugen, MD; John K. Maher, MD; Timothy W. Deakers, MD, PhD
Objective: To determine if inhaled albuterol (salbutamol) increases oxygen consumption (V′o2) in children and, if so, the duration of this effect. Design: Oxygen consumption was measured by indirect calorimetry using the Argon dilution technique with a respiratory mass spectrometer. After measurement of baseline values, albuterol was administered and subsequent measurements were performed at 10 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. Setting: Multidisciplinary PICU in a university teaching hospital. Patients: Eleven intubated infants and children (five girls, six boys) with a mean age of 20 months (range, 1 mo to 8 yr) and a mean weight of 10.7 kg (range, 3.1–23 kg) who required therapeutic albuterol inhalations. Intervention: Nine hundred micrograms of albuterol (10 puffs) was administered by a metered-dose inhaler into a spacer through the inspiratory arm of the ventilator circuit near to the patient, during 10 mechanically assisted breaths. Measurements and Main Results: All children showed an increase in V′o2 within 10 minutes (mean increase 48.6%). The increased V′o2 was still elevated (42.3% above baseline) at 1 hour, but 3 hours after albuterol inhalation, the V′o2 was back to baseline in all patients. Heart rate increased significantly at 10 minutes, 1 hour, and 2 hours after inhalation. Conclusion: There is a large increase in V′o2 after albuterol inhalation. This effect lasts up to 3 hours. (Pediatr Crit Care Med 2014; 15:e389–e392) All authors: Division of Critical Care, Children’s Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, CA. Current address for Dr. Hugen: Department of Respiratory Medicine and Allergy, Radboud University Nijmegen Medical Centre, Amalia Children’s Hospital, Nijmegen, The Netherlands. Current address for Dr. Maher: Division of Critical Care, Driscoll Children’s Hospital, Corpus Christi, TX. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Patrick A. Ross, MD, PICU Administration, MS #12, Children’s Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027. E-mail: [email protected] Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000000279
Pediatric Critical Care Medicine
Key Words: albuterol inhalation; bronchodilator; children; mechanical ventilation; oxygen consumption; salbutamol
I
nhaled albuterol, a β-agonist, is widely used in the management of asthma in children. Recent reports have shown elevated serum lactate levels in children receiving albuterol for asthma (1–3). The elevated lactate occurred in the presence of normal oxygen delivery leading the authors to question whether the effect was due to β-adrenergic stimulation (2). It has been known for some time that epinephrine (adrenaline) and albuterol (salbutamol) have a stimulating effect in human adults on minute volume of ventilation (V′E) and oxygen consumption (V′o2) (4–7). We have previously demonstrated a marked increase in V′E (mean, 82%) and V′o2 (mean, 46.5%) in anesthetized, intubated, and spontaneously breathing Rhesus monkeys after inhalation of albuterol (8). This metabolic response appeared to be a “class” effect of β-adrenergic drugs as it occurred after several additional β-agonists but was not seen after ipratropium bromide, cromolyn sodium, or theophylline (8). Further, the metabolic response to albuterol in the Rhesus monkey was fully suppressed by the nonselective β-adrenergic blocker, propranolol (9). The effect of albuterol on oxygen consumption has not been previously reported in children. The aim of this study was to determine if inhaled albuterol increases oxygen consumption in infants and children and, if so, the duration of this effect.
MATERIALS AND METHODS This study was conducted in a multidisciplinary PICU on 11 infants and children who required therapeutic albuterol inhalations. Only children with cuffed endotracheal tubes (ETTs) were included because an absence of an air leak was needed for accurate measurements of gas exchange. The patients received sedation titrated to adequate effect based on nursing and physician observation. The study was approved by the investigational review board, and informed consent was obtained from the parents in each case. Oxygen consumption (V′o2), carbon dioxide production (V′co2), minute ventilation (V′E), and respiratory quotient www.pccmjournal.org
e389
Ross et al
were measured by indirect calorimetry using the Argon dilution technique with a respiratory mass spectrometer (Airspec MGA 2200, Biggin Hill, United Kingdom) (10). We have previously reported the measurement of expired gases from the ETT using an isolation valve in this manner (11–13). Vital signs were recorded including heart rate, respiratory rate, oxygen saturation by pulse oximetry, end-tidal carbon dioxide, and temperature by rectal probe. After measurement of baseline values, 900 μg of albuterol (10 puffs) was administered by a metered-dose inhaler into a spacer (A.C.E. Diemolding Healthcare Division, Canastota, NY) (14) through the inspiratory arm of the ventilator circuit near to the patient, during 10 mechanically assisted breaths. Subsequent measurements were performed at 10 minutes, 1 hour, 2 hours, 3 hours, and 4 hours after administration.
shows the mean values ± sd, and the mean percent change from baseline, for V′o2, V′E, and heart rate before and 10 minutes, 1 hour, 2 hours, and 3 hours after inhalation of albuterol. Data are presented only to 3 hours as mean values had returned to baseline. Changes in V′o2, V′E, and heart rate are presented graphically in Figure 1. Following albuterol inhalation, there was an increase in V′o2 within 10 minutes for all patients. V′o2 was increased further at the 1-hour measurement and returned to baseline by 3 hours. The change in V′o2 was statistically significant at 10 minutes and 1 hour after albuterol inhalation. The heart rate was increased significantly at 10 minutes, 1 hour, and 2 hours after albuterol. No significant changes in V′E were found.
Statistical Analysis Mean percent changes between baseline and post inhalation values were compared by analysis of variance with Bonferroni correction (Statistica, Microsoft Corporation, Richmond, WA). Each patient served as his or her own control. A p value less than or equal to 0.05 was considered significant.
This study demonstrates that inhaled albuterol causes a marked increase in oxygen consumption in infants and children. This is consistent with previous observations in monkeys (8, 9) and adults (6). The increase of V′o2 within 10 minutes was rapid but consistent with reports on the pharmacokinetics of albuterol (15). The maximum increase in V′o2 was reached in all subjects by 1 hour. The duration of the effect was, on average, complete by 3 hours although in some individuals lasted up to 4 hours. The increase in heart rate followed a similar pattern, but the increase was significant up to 2 hours. The change in heart rate was not a novel finding but showed that the method for administration with albuterol in the ventilator circuit was effective. The absence of a change in V′E probably occurred as a result of the patients being studied were either sedated while
RESULTS Eleven children were included, five girls and six boys. The mean age was 20 months, with a range from 1 month to 8 years. Their mean weight was 10.7 kg (range, 3.1–23 kg). Table 1 shows the patient characteristics. All patients were on low ventilator settings, with an Fio2 of 0.45 or less. Table 2 Table 1. Patient
DISCUSSION
Patient Characteristics for 11 Children Receiving Albuterol Sex
Age (yr)
Weight (kg)
Diagnosis
Fio2
Ventilator Settings
Sedation
1
Female
2 1/12
15
Seizures, asthma
0.4
CPAP = 4
Phenobarbital, diazepam
2
Female
2 3/12
16
Pneumonia, RSV+
0.4
CPAP = 4
Morphine, diazepam
3
Female
8 1/12
23
Fibrotic lung disease
0.35
PS = 12; PEEP = 4
Fentanyl, midazolam
4
Male
1/12
3.9
Pneumonia
0.45
SIMV/PC; rate = 12/ min, PIP = 26; PEEP = 4
Morphine, diazepam
5
Male
3/12
6.1
Pneumonia
0.45
SIMV/PC; rate = 16 /min, PIP = 28; PEEP = 4
6
Male
1 5/12
11.6
Pneumonia
0.4
CPAP = 4
Fentanyl, midazolam
7
Female
3/12
5
Pneumonia, RSV+
0.4
CPAP = 4
Fentanyl, midazolam
8
Male
1/12
3.1
Congenital lobar emphysema status post lobectomy
0.4
PS = 8, PEEP = 4; rate = 6/min
9
Female
1 3/12
8.2
Bronchiolitis/RSV + BPD
0.4
CPAP = 2
Fentanyl, midazolam, pentobarbital
10
Male
3 10/12
19.4
Pneumonia
0.4
SIMV/PC; rate = 24/ min, PIP = 34; PEEP = 4
Fentanyl, diazepam, vecuronium
11
Male
1 1/12
6.3
Viral pneumonia, BPD
0.4
PS = 12; rate = 12 / min, PEEP = 6
Fentanyl, midazolam pentobarbital
Diazepam
Morphine
CPAP = continuous positive airway pressure, RSV = respiratory syncytial virus, PS = pressure support, PEEP = positive end-expiratory pressure, SIMV = synchronized intermittent mandatory ventilation, PC = pressure control, PIP = peak inspiratory pressure, BPD = bronchopulmonary dysplasia.
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Online Brief Report
Table 2. Mean Oxygen Consumption, Volume of Ventilation, and Heart Rate (±sd) and Percent Change From Baseline at 10 Minutes, 1 Hour, 2 Hours, and 3 Hours After Inhalation of Albuterol Measurements
Baseline Before Albuterol
10 Min Post Albuterol
1 Hr Post Albuterol
2 Hr Post Albuterol
3 Hr Post Albuterol
Oxygen consumption (mL/min/kg)
8.23 ± 3.95
12.23 ± 6.34
11.71 ± 4.22
9.59 ± 4.7
Δ % (from baseline)
0
48.6a
42.3a
16.5
–14.5
Volume of ventilation (mL/min/kg)
371.0 ± 2.47
390.7 ± 2.37
385.0 ± 2.32
366.4 ± 2.13
361.7 ± 2.01
Δ % (from baseline)
0
5.3
3.8
–1.3
–2.5
121 ± 19
148 ± 18
145 ± 21
143 ± 17
133 ± 17
0
22.3
19.8
18.2
Heart rate (beats/min) Δ % (from baseline)
a
a
a
7.04 ± 4.28
9.9
p < 0.05.
a
Figure 1. Mean percentage change in oxygen consumption (V′o2), minute ventilation, and heart rate 10 min, 1 hr, 2 hr, and 3 hr after inhalation of albuterol. Data were compared by analysis of variance with Bonferroni correction (*p < 0.05). Of note, the significant value at 120 min was heart rate and not V′o2. V′E = volume of ventilation.
breathing spontaneously through the ETT or under neuromuscular blockade on fixed ventilator settings. The large increase in oxygen consumption we found with albuterol use has clinical implications in a PICU setting. Patients with critical asthma who are receiving large doses of albuterol as with a continuous inhalation often have ongoing tachycardia. Further, these patients have been found to have elevated serum lactate levels. It is difficult to identify whether the tachycardia and elevated lactate are related to their disease process or a result of ongoing β-adrenergic stimulation. By increasing oxygen consumption, large doses of albuterol may be causing harm and alternative medications such as Levalbuterol may bear consideration. Potential mechanisms for the increase in V′o2 after albuterol inhalation are the effects of albuterol on bronchi (dilatation) and increasing minute ventilation (7), increasing heart rate (16), Pediatric Critical Care Medicine
glycogenolysis and calorigenesis (17), skeletal muscle tremor (18), and direct effects on cellular metabolism. Albuterol acting at the cellular sodium-potassium-ATPase pump for the treatment of hyperkalemia has been shown to be effective within 30–60 minutes (19, 20). In our present study, albuterol caused a significant increase in heart rate, which may have contributed to the increased V′o2. We did not observe a change in minute ventilation or tremor, and we were unable to measure cellular effects. The results of the study must be viewed in light of possible limitations. There were a limited number of patients enrolled. The disease processes, sedation, and modes of mechanical ventilation varied. We did not attempt to control the patient’s temperature but as is standard in a PICU, room temperature remained constant during the measurements which were completed in 4 hours. The albuterol dosage was higher than others may choose in their clinical practice. However, this is a dose that we used clinically and was chosen to allow for the delivery method and the potential for condensation of drug on the ventilator tubing. One additional limitation is that for patients with asthma, a transient fall in arterial oxygen tension has been observed after inhalation of β2-agonist bronchodilators. The mechanism of this acute decline in oxygenation has been assumed to reflect increased mismatch of ventilation to perfusion. As all of these patients were receiving supplemental oxygen, we cannot assess whether the increase in V′o2 as a direct effect of albuterol could contribute to a fall in arterial oxygen tension. In conclusion, we found a large increase in V′o2 in children receiving inhaled albuterol. The effect was present in 10 minutes and lasted up to 3 hours after a single inhaled dose. Further research will be necessary to determine if this effect contributes to the development of elevate serum lactate or other side effects seen with albuterol use.
REFERENCES
1. Koul PB, Minarik M, Totapally BR: Lactic acidosis in children with acute exacerbation of severe asthma. Eur J Emerg Med 2007; 14:56–58 www.pccmjournal.org
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November 2014 • Volume 15 • Number 9
