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Review Article
Respiratory depression caused by low dose of olanzapine: A case report
Depresión respiratoria causada por dosis baja de Olanzapina: informe de un caso
Masatoshi Inoue
Tsushima City Hospital, postcode:496-8537, 3-73 Tachibana-cho, Tsushima-city, Aichi, Japan
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    "titulo" => "Respiratory depression caused by low dose of olanzapine&#58; A case report"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Olanzapine&#44; which is known as multi-acting receptor targeted antipsychotics &#40;MARTA&#41;&#44; is widely used throughout the world to treat patients with schizophrenia and bipolar disorder&#46; Olanzapine has high affinity for serotonin&#44; dopamine&#44; alpha1-adrenergic&#44; histamine H1&#44; and muscarinic receptors and exhibits antidopaminergic&#44; antiserotonergic&#44; and antimuscarinic effects&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> The main symptoms of olanzapine intoxication are decreased consciousness&#44; hypotension&#44; tachycardia&#44; and excessive salivation&#44; and usually symptomatic and supportive treatment is given&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> However&#44; to our knowledge&#44; respiratory depression has not been reported with doses as low as 5&#8239;mg&#46; This study reports the case of an elderly woman with severe hypercarbia&#44; hypoxia&#44; and impaired consciousness possibly due to low doses of oral olanzapine&#46; We expect that this case report will add to the existing body of literature on the appropriate use of olanzapine&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Clinical case</span><p id="p0010" class="elsevierStylePara elsevierViewall">A 78-year-old woman presented to the emergency department with impaired consciousness and hypoxia&#46; She had a history of schizophrenia which had been treated with olanzapine 5&#8239;mg&#47;day and valproic acid 200&#8239;mg&#47;day for approximately 2 years in a psychiatrist&#39;s office&#46; She had no medical or surgical history&#46; She had no history of addiction&#44; and her medications were properly administered by family members&#46; Her Glasgow Coma Scale &#40;GCS&#41; score was E3V4M4&#44; body temperature was 36&#46;6&#8239;&#176;C&#44; blood pressure was 94&#47;66&#8239;mmHg&#44; respiratory rate was 14 breaths per minute&#44; heart rate was 69 beats per minute&#44; and oxygen saturation was 78&#37; &#40;room air&#41;&#46; The surface electrocardiogram revealed a right bundle branch block&#46; Transthoracic echocardiography showed normal cardiac function with an estimated ejection fraction of 60&#37;&#46; Chest X-ray revealed cardiomegaly with a cardio-thoracic ratio of 57&#46;6&#37; and pulmonary congestion&#46; Head computed tomography was unremarkable&#46; Arterial blood gas evaluation revealed severe hypoxemia&#44; chronic respiratory acidosis&#44; and metabolic alkalosis &#40;pH&#8239;7&#46;41&#59; pO2 65&#46;3&#8239;mmHg&#59; PaCO2 82&#46;7&#8239;mmHg&#59; HCO3 46&#46;8&#8239;mmol&#47;L&#41;&#46; Multiple nasal swab PCR tests for COVID-19 were negative&#46; We diagnosed her for congestive heart failure and put on non-invasive positive-pressure ventilation &#40;NPPV&#41; with spontaneous&#47;timed mode &#40;FiO2 1&#46;0&#59; inspiratory positive airway pressure 10&#8239;cmH<span class="elsevierStyleInf">2</span>O&#59; expiratory positive airway pressure 5&#8239;cmH<span class="elsevierStyleInf">2</span>O&#41; in the emergency room&#46; We suggested endotracheal intubation&#44; but she and her family refused&#46; We admitted her to the high care unit&#44; treating her with intravenous bolus furosemide 40&#8239;mg&#47;day&#44; normal saline&#44; and potassium chloride&#46; All oral medications were discontinued&#46; Serum renin was 0&#46;2 &#40;ng&#47;mL&#47;h&#44; normal&#59; 0&#46;3&#8211;3&#46;9&#41; and aldosterone was 4&#46;0 &#40;pg&#47;mL&#44; normal&#59; 40&#8211;82&#46;1&#41;&#44; ruling out primary aldosteronism&#46; Because her breathing was shallow and slow &#40;median tidal volume was 220&#8239;mL and respiratory rate was 14 breaths per minute&#41;&#44; hypercarbia did not improve readily &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; Her level of consciousness gradually improved and her breathing became deeper and deeper&#46; She was weaned from NPPV on day 19&#46; She was discharged on day 30&#46; Valproic acid was resumed after discharge from hospital&#44; but the patient has progressed without recurrence&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Discussion</span><p id="p0015" class="elsevierStylePara elsevierViewall">Olanzapine has an average half-life of 33&#8239;h in healthy individuals&#44; but longer in elderly patients&#44; women&#44; and non-smokers&#46;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> Although there have been a few reports of olanzapine causing respiratory depression&#44; most have been at very high doses&#44; and this paper classifies 120&#8211;840&#8239;mg as moderate poisoning&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> As far as we know&#44; the lowest dose of olanzapine to cause coma was 20&#8239;mg&#47;day&#44; but this case did not cause respiratory depression&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> The patient was an elderly non-smoking woman&#44; who may have decreased clearance and increased blood levels of olanzapine&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">In a multicenter&#44; randomized&#44; double-blind&#44; placebo-controlled study of 356 patients taking olanzapine 5&#8239;mg for 4&#8239;days in Japan&#44; no cases of serious side effects&#44; including respiratory depression&#44; were observed&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> In this case report&#44; olanzapine caused edema that took 2&#8239;weeks to improve after discontinuation&#46;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> Our case took about the same amount of time&#46; These findings suggest that olanzapine is accumulative and may take a long time to clear from the body when taken orally over a long period of time&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">There is no accepted antidote for the side effects of olanzapine&#44; and hemodialysis does not remove olanzapine&#46;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> However&#44; it has been reported that flumazenil<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> or an intravenous infusion of the lipid<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> has improved the symptoms caused by olanzapine&#46; These treatments are relatively harmless&#44; it would have been worth trying in this case&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">An arterial blood gas test showed that HCO<span class="elsevierStyleInf">3</span> was markedly elevated and pH was almost normal on admission&#46; Because hypochlorhydria and hypokalemia also produce chronic metabolic alkalosis&#44; we started electrolyte correction from the time of admission&#46;<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> Metabolic alkalosis persisted after electrolyte improvement&#44; but acid&#8211;base balance tended to improve after resolution of respiratory depression&#46; Based on the course of events&#44; we concluded that the acid&#8211;base imbalance began with olanzapine-induced respiratory depression&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">She was elderly with dementia and may have been unaware of her symptoms&#46; If somnolence is observed in a patient taking olanzapine&#44; a blood gas should be obtained and appropriate respiratory care should be provided&#46; Elderly patients&#44; women&#44; and non-smokers may have elevated olanzapine concentrations and may do better with lower than usual doses&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Author&#39;s Contribution</span><p id="p0040" class="elsevierStylePara elsevierViewall">Conception and design of study&#44; Acquisition of data&#44; Analysis and&#47;or interpretation of data&#44; Drafting the manuscript&#44; Revising the manuscript critically for important intellectual content&#44; and Approval of the version of the manuscript to be published&#58; M&#46; Inoue&#46;</p></span></span>"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Objective</span><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Olanzapine is widely used throughout the world to treat patients with schizophrenia and bipolar disorder&#46; Olanzapine has numerous side effects&#44; but respiratory depression has not been reported with doses as low as 5&#8239;mg&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Clinical case</span><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">An elderly woman presented with severe hypercarbia&#44; hypoxia&#44; and impaired consciousness possibly due to low doses of oral olanzapine&#46; There is no accepted antidote for the side effects of olanzapine&#44; so we followed the patient with respiratory support and electrolyte correction&#46; Symptoms improved after 2&#8239;weeks and did not recur&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results and conclusions</span><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Elderly patients&#44; women&#44; and non-smokers may have elevated olanzapine concentrations and may do better with lower than usual doses&#46; If somnolence is observed in a patient taking olanzapine&#44; a blood gas should be obtained and appropriate respiratory care should be provided&#46; We expect that this case report will add to the existing body of literature on the appropriate use of olanzapine&#46;</p></span>"
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        "resumen" => "<span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Objetivo</span><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Olanzapina se utiliza de manera amplia a nivel mundial para tratar a los pacientes con esquizofrenia y trastorno bipolar&#46; Tiene numerosos efectos secundarios&#44; pero no se hab&#237;a reportado depresi&#243;n respiratoria con dosis bajas de 5&#8239;mg&#46;</p></span> <span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Caso cl&#237;nico</span><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Una mujer mayor acudi&#243; con hipercarbia severa&#44; hipoxia y deterioro de la consciencia&#44; debido posiblemente a la administraci&#243;n de dosis bajas de olanzapina oral&#46; No existe ant&#237;doto aceptado para los efectos secundarios de olanzapina&#44; por lo que seguimos a la paciente con soporte respiratorio y correcci&#243;n de electrolitos&#46; Los s&#237;ntomas mejoraron transcurridas dos semanas&#44; no produci&#233;ndose recidiva&#46;</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Resultados y conclusiones</span><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Los pacientes mayores&#44; mujeres&#44; y no fumadores pueden tener concentraciones elevadas de olanzapina&#44; siendo adecuado utilizar dosis m&#225;s bajas de lo habitual&#46; De observarse somnolencia en un paciente que toma olanzapina&#44; deber&#225;n obtenerse gases sangu&#237;neos&#44; y aportarse cuidados respiratorios adecuados&#46; Esperamos que este informe de caso ayude al cuerpo existente de la literatura con relaci&#243;n al uso adecuado de olanzapina&#46;</p></span>"
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                  \t\t\t\t">pCO2 &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#8211;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HCO3 &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#46;6&#8211;26&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sodium &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">138&#8211;146&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">145&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">149&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">140&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">138&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Potassium &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">3&#46;6&#8211;4&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">3&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">3&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chloride &#40;mmol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#8211;109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">97&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">99&#46;9&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Laboratory investigations for the patient&#46; Blood gas data is venous&#46;</p>"
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                            0 => "F&#46;P&#46; Bymaster"
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                            2 => "J&#46;F&#46; Falcone"
                            3 => "R&#46;D&#46; Marsh"
                            4 => "N&#46;A&#46; Moore"
                            5 => "N&#46;C&#46; Tye"
                            6 => "P&#46; Seeman"
                            7 => "D&#46;T&#46; Wong"
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                        "tituloSerie" => "Neuropsychopharmacology&#46;"
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                        "volumen" => "14"
                        "numero" => "2"
                        "paginaInicial" => "87"
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Article information
ISSN: 11345934
Original language: English
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