American Journal of Emergency Medicine 33 (2015) 312.e3–312.e4
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation☆,☆☆ Abstract A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2, 64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation. A 74-year-old man was referred to our hospital due to progressive deterioration of his level of consciousness during the last 2 days and desaturation. His history was significant for a stroke, 27 years earlier, with residual right-sided hemiparesis and limited functional reserve (modified Rankin scale score, 4). In the previous 2 years, he had had neuropathic pain, initially treated with pregabalin with significant side effects, and in the last 2 weeks, he was managed with transdermal fentanyl patch (75 μg every 72 hours). He also self-administered tramadol (50 mg, twice to thrice daily) for recurrent breakthrough pain. On evaluation, his vital signs were as follows: arterial blood pressure, 145/80 mm Hg; heart rate, 102 beats per minute; respiratory rate, 28 breaths per minute; and temperature, 37.8°C. His pupils were constricted with a brisk response to light. His Glasgow Coma Scale (GCS) score was 6, and further neurologic examination revealed a right-sided focal neurologic deficit. Arterial blood gas (ABG) examination on supplemental oxygen yielded the following values: pH 7.15; PCO2, 133 mm Hg; PO 2, 64 mm Hg; and H CO3 , 31 mmol/L. Lung auscultation and chest radiograph were negative for significant findings. Renal and hepatic biochemistry was normal, but a toxicology screen could not be performed. The fentanyl patch was
☆ Funding: None. ☆☆ Conflict of interest: None for all authors. 0735-6757/© 2014 Elsevier Inc. All rights reserved.
immediately removed, and a dose of 0.4 mg of naloxone was administered intravenously. Within 5 minutes, his GCS increased to 15, whereas his ABG values also improved: pH 7.21; PCO2, 105 mm Hg; PO2, 77 mm Hg; and HCO3 30 mmol/L (on Venturi mask, 28%). He was immediately started on noninvasive ventilation (NIV) via a face mask using the average volume-assured pressure support mode with the following settings: inspiratory positive airway pressure (IPAP) minimum (min), 15 cm H2O; IPAP maximum (max), 24 cm H2O; expiratory positive airway pressure (EPAP), 6 cm H2O; back-up respiratory rate, 25 breaths per minute; and tidal volume, 540 mL. Supplemental oxygen was administered via the circuit at a rate 3.5 L/min to ensure an oxygen saturation as measured by pulse oximetry more than 88%. Another 0.4 mg of naloxone was administered after 1 hour when his GCS dropped to 11. After these interventions, the patient displayed a quick improvement in ABG values within the next 6 hours (Figure). Supplemental oxygen was uneventfully discontinued on day 3, but despite this initial improvement, the patient failed to wean from NIV in the following 2 weeks, due to persistent hypercapnia and acidosis, and he was finally discharged on a home mechanical ventilation prescription. A sleep study excluded the coexistence of obstructive sleep apnea syndrome, and a brain magnetic resonance imaging was negative for new findings. This is a case of acute drug-induced hypercapnic acidosis superimposed on a background of chronic ventilatory insufficiency as evidenced by the increased initial bicarbonate concentration and the patient’s failure to wean from NIV after initial stabilization. This ventilatory insufficiency could be a result of chronic opioid intoxication [1], although it could also be attributed to the long-term respiratory pump sequelae observed in poststroke patients with impaired functional performance [2]. The diagnosis of drug-induced respiratory depression was based on the patient's drug history and his prompt clinical improvement after naloxone administration. Tramadol is only partially antagonized by naloxone, and reports on naloxone's efficiency in tramadolintoxicated patients have been inconsistent [3]. On the other hand, fentanyl when delivered transdermally, has a prolonged half-life, and repeated naloxone dosing or even continuous administration is often necessary [4]; eventually, orotracheal intubation might be required in some patients [5]. Our patient quickly regained consciousness after a single dose of naloxone, whereas his severe respiratory acidosis only moderately improved. Nevertheless, the administration of naloxone created a “therapeutic window” that obviated the need for orotracheal intubation and bought time for NIV to gradually lower carbon dioxide and control respiratory acidosis. Importantly, institution of NIV allowed for periods of prolonged in-hospital ventilatory support, something that would not have been without increased risks (eg,
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M. Agrafiotis et al. / American Journal of Emergency Medicine 33 (2015) 312.e3–312.e4
Figure. Improvement in pH and PCO2 in the first 6 hours after institution of NIV. Dotted line is for pH, and solid line is for PCO2.
Michalis Agrafiotis, MD ⁎ Stavros Tryfon, MD, PhD Demetra Siopi, MD Georgia Chassapidou, MD Artemis Galanou, MD Venetia Tsara, MD, PhD Department of Pulmonary Medicine, “Georgios Papanikolaou” General Hospital of Thessaloniki Exohi, Thessaloniki, Greece ⁎Corresponding author. Department of Pulmonary Medicine “Georgios Papanikolaou” General Hospital of Thessaloniki G. Papanikolaou Ave, 57010 Exohi, Thessaloniki, Greece Tel.: + 30 2310276929; fax: + 30 2310358470. E-mail address: m.agrafi[email protected] http://dx.doi.org/10.1016/j.ajem.2014.08.006
infections) in the case of invasive mechanical ventilation [6]. Last, acute NIV administration also functioned as an intermediate management stage, which facilitated long-term planning of home mechanical ventilatory support. This combination of antidote and NIV in the management of opiate-induced respiratory complications has also been appreciated in previous reports [7,8]. In both of these cases, severe respiratory depression in addition to noncardiogenic pulmonary edema was caused by methadone overdose. Although invasive ventilation is traditionally considered the standard treatment for life-threatening drug-induced hypercapnic acidosis, its complications cannot be overlooked, especially in patients with limited functional reserve. In the last few years, NIV has witnessed expanding indications and presents an attractive alternative, which can reduce the requirement of orotracheal intubation with its associated risks and provide effective ventilatory support for prolonged periods of in-hospital management. This benefit might be of particular importance for frail patients who are commonly treated with opioids for chronic pain [9].
References [1] Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Sullivan MD, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med 2010;152(2):85–92. [2] Pinheiro MB, Polese JC, Faria CD, Machado GC, Parreira VF, Britto RR, et al. Inspiratory muscular weakness is most evident in chronic stroke survivors with lower walking speeds. Eur J Phys Rehabil Med 2014;50(3):301–7. [3] Spiller HA, Gorman SE, Villalobos D, Benson BE, Ruskosky DR, Stancavage MM, et al. Prospective multicenter evaluation of tramadol exposure. J Toxicol Clin Toxicol 1997;35(4):361–4. [4] Lyttle MD, Verma S, Isaac R. Transdermal fentanyl in deliberate overdose in pediatrics. Pediatr Emerg Care 2012;28(5):463–4. [5] Boyer EW. Management of opioid analgesic overdose. N Engl J Med 2012;367(2):146–55. [6] Girou E, Schortgen F, Delclaux C, Brun-Buisson C, Blot F, Lefort Y, et al. Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients. JAMA 2000;284(18):2361–7. [7] Ridgway ZA, Pountney AJ. Acute respiratory distress syndrome induced by oral methadone managed with non-invasive ventilation. Emerg Med J 2007;24(9):681. [8] Gonzva J, Prunet B, Deniel C, Benner P, Toppin F, Brun PM. Early antidote use associated with noninvasive ventilation in prehospital treatment of methadone intoxication. Am J Emerg Med 2013;31(2):448.e5-6. [9] Dahan A, Overdyk F, Smith T, Aarts L, Niesters M. Pharmacovigilance: a review of opioid-induced respiratory depression in chronic pain patients. Pain Physician 2013;16(2):E85–94.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation☆,☆☆ Abstract A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2, 64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation. A 74-year-old man was referred to our hospital due to progressive deterioration of his level of consciousness during the last 2 days and desaturation. His history was significant for a stroke, 27 years earlier, with residual right-sided hemiparesis and limited functional reserve (modified Rankin scale score, 4). In the previous 2 years, he had had neuropathic pain, initially treated with pregabalin with significant side effects, and in the last 2 weeks, he was managed with transdermal fentanyl patch (75 μg every 72 hours). He also self-administered tramadol (50 mg, twice to thrice daily) for recurrent breakthrough pain. On evaluation, his vital signs were as follows: arterial blood pressure, 145/80 mm Hg; heart rate, 102 beats per minute; respiratory rate, 28 breaths per minute; and temperature, 37.8°C. His pupils were constricted with a brisk response to light. His Glasgow Coma Scale (GCS) score was 6, and further neurologic examination revealed a right-sided focal neurologic deficit. Arterial blood gas (ABG) examination on supplemental oxygen yielded the following values: pH 7.15; PCO2, 133 mm Hg; PO 2, 64 mm Hg; and H CO3 , 31 mmol/L. Lung auscultation and chest radiograph were negative for significant findings. Renal and hepatic biochemistry was normal, but a toxicology screen could not be performed. The fentanyl patch was
☆ Funding: None. ☆☆ Conflict of interest: None for all authors. 0735-6757/© 2014 Elsevier Inc. All rights reserved.
immediately removed, and a dose of 0.4 mg of naloxone was administered intravenously. Within 5 minutes, his GCS increased to 15, whereas his ABG values also improved: pH 7.21; PCO2, 105 mm Hg; PO2, 77 mm Hg; and HCO3 30 mmol/L (on Venturi mask, 28%). He was immediately started on noninvasive ventilation (NIV) via a face mask using the average volume-assured pressure support mode with the following settings: inspiratory positive airway pressure (IPAP) minimum (min), 15 cm H2O; IPAP maximum (max), 24 cm H2O; expiratory positive airway pressure (EPAP), 6 cm H2O; back-up respiratory rate, 25 breaths per minute; and tidal volume, 540 mL. Supplemental oxygen was administered via the circuit at a rate 3.5 L/min to ensure an oxygen saturation as measured by pulse oximetry more than 88%. Another 0.4 mg of naloxone was administered after 1 hour when his GCS dropped to 11. After these interventions, the patient displayed a quick improvement in ABG values within the next 6 hours (Figure). Supplemental oxygen was uneventfully discontinued on day 3, but despite this initial improvement, the patient failed to wean from NIV in the following 2 weeks, due to persistent hypercapnia and acidosis, and he was finally discharged on a home mechanical ventilation prescription. A sleep study excluded the coexistence of obstructive sleep apnea syndrome, and a brain magnetic resonance imaging was negative for new findings. This is a case of acute drug-induced hypercapnic acidosis superimposed on a background of chronic ventilatory insufficiency as evidenced by the increased initial bicarbonate concentration and the patient’s failure to wean from NIV after initial stabilization. This ventilatory insufficiency could be a result of chronic opioid intoxication [1], although it could also be attributed to the long-term respiratory pump sequelae observed in poststroke patients with impaired functional performance [2]. The diagnosis of drug-induced respiratory depression was based on the patient's drug history and his prompt clinical improvement after naloxone administration. Tramadol is only partially antagonized by naloxone, and reports on naloxone's efficiency in tramadolintoxicated patients have been inconsistent [3]. On the other hand, fentanyl when delivered transdermally, has a prolonged half-life, and repeated naloxone dosing or even continuous administration is often necessary [4]; eventually, orotracheal intubation might be required in some patients [5]. Our patient quickly regained consciousness after a single dose of naloxone, whereas his severe respiratory acidosis only moderately improved. Nevertheless, the administration of naloxone created a “therapeutic window” that obviated the need for orotracheal intubation and bought time for NIV to gradually lower carbon dioxide and control respiratory acidosis. Importantly, institution of NIV allowed for periods of prolonged in-hospital ventilatory support, something that would not have been without increased risks (eg,
312.e4
M. Agrafiotis et al. / American Journal of Emergency Medicine 33 (2015) 312.e3–312.e4
Figure. Improvement in pH and PCO2 in the first 6 hours after institution of NIV. Dotted line is for pH, and solid line is for PCO2.
Michalis Agrafiotis, MD ⁎ Stavros Tryfon, MD, PhD Demetra Siopi, MD Georgia Chassapidou, MD Artemis Galanou, MD Venetia Tsara, MD, PhD Department of Pulmonary Medicine, “Georgios Papanikolaou” General Hospital of Thessaloniki Exohi, Thessaloniki, Greece ⁎Corresponding author. Department of Pulmonary Medicine “Georgios Papanikolaou” General Hospital of Thessaloniki G. Papanikolaou Ave, 57010 Exohi, Thessaloniki, Greece Tel.: + 30 2310276929; fax: + 30 2310358470. E-mail address: m.agrafi[email protected] http://dx.doi.org/10.1016/j.ajem.2014.08.006
infections) in the case of invasive mechanical ventilation [6]. Last, acute NIV administration also functioned as an intermediate management stage, which facilitated long-term planning of home mechanical ventilatory support. This combination of antidote and NIV in the management of opiate-induced respiratory complications has also been appreciated in previous reports [7,8]. In both of these cases, severe respiratory depression in addition to noncardiogenic pulmonary edema was caused by methadone overdose. Although invasive ventilation is traditionally considered the standard treatment for life-threatening drug-induced hypercapnic acidosis, its complications cannot be overlooked, especially in patients with limited functional reserve. In the last few years, NIV has witnessed expanding indications and presents an attractive alternative, which can reduce the requirement of orotracheal intubation with its associated risks and provide effective ventilatory support for prolonged periods of in-hospital management. This benefit might be of particular importance for frail patients who are commonly treated with opioids for chronic pain [9].
References [1] Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Sullivan MD, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med 2010;152(2):85–92. [2] Pinheiro MB, Polese JC, Faria CD, Machado GC, Parreira VF, Britto RR, et al. Inspiratory muscular weakness is most evident in chronic stroke survivors with lower walking speeds. Eur J Phys Rehabil Med 2014;50(3):301–7. [3] Spiller HA, Gorman SE, Villalobos D, Benson BE, Ruskosky DR, Stancavage MM, et al. Prospective multicenter evaluation of tramadol exposure. J Toxicol Clin Toxicol 1997;35(4):361–4. [4] Lyttle MD, Verma S, Isaac R. Transdermal fentanyl in deliberate overdose in pediatrics. Pediatr Emerg Care 2012;28(5):463–4. [5] Boyer EW. Management of opioid analgesic overdose. N Engl J Med 2012;367(2):146–55. [6] Girou E, Schortgen F, Delclaux C, Brun-Buisson C, Blot F, Lefort Y, et al. Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients. JAMA 2000;284(18):2361–7. [7] Ridgway ZA, Pountney AJ. Acute respiratory distress syndrome induced by oral methadone managed with non-invasive ventilation. Emerg Med J 2007;24(9):681. [8] Gonzva J, Prunet B, Deniel C, Benner P, Toppin F, Brun PM. Early antidote use associated with noninvasive ventilation in prehospital treatment of methadone intoxication. Am J Emerg Med 2013;31(2):448.e5-6. [9] Dahan A, Overdyk F, Smith T, Aarts L, Niesters M. Pharmacovigilance: a review of opioid-induced respiratory depression in chronic pain patients. Pain Physician 2013;16(2):E85–94.
